T cells are a type of lymphocyte that play a significant role in the adaptive immune system of horses. They are involved in identifying and responding to pathogens, such as viruses and bacteria, by recognizing specific antigens. T cells can be categorized into various subsets, including helper T cells (CD4+), cytotoxic T cells (CD8+), and regulatory T cells, each with specific functions in immune regulation and response. The study of T cells in horses encompasses their development, activation, and the mechanisms by which they mediate immune responses. This research area includes investigations into how T cells contribute to equine health, their response to vaccinations, and their involvement in immune-mediated diseases. This page compiles peer-reviewed research studies and scholarly articles that explore the biology, function, and clinical relevance of T cells in equine immunology.
Bergmann T, Lindvall M, Moore E, Moore E, Sidney J, Miller D, Tallmadge RL, Myers PT, Malaker SA, Shabanowitz J, Osterrieder N, Peters B, Hunt DF....Quantitative peptide-binding motifs of MHC class I alleles provide a valuable tool to efficiently identify putative T cell epitopes. Detailed information on equine MHC class I alleles is still very limited, and to date, only a single equine MHC class I allele, Eqca-1*00101 (ELA-A3 haplotype), has been characterized. The present study extends the number of characterized ELA class I specificities in two additional haplotypes found commonly in the Thoroughbred breed. Accordingly, we here report quantitative binding motifs for the ELA-A2 allele Eqca-16*00101 and the ELA-A9 allele Eqca-1*00201. Uti...
Colbath AC, Dow SW, Phillips JN, McIlwraith CW, Goodrich LR.The use of allogeneic bone marrow-derived mesenchymal stem cells (BMDMSCs) may provide an effective alternative to autologous BMDMSCs for treatment of equine musculoskeletal injuries. However, concerns have been raised regarding the potential safety and effectiveness of allogeneic BMDMSCs. We conducted studies to assess the immunological properties of equine allogeneic BMDMSCs compared with those of autologous BMDMSCs. For assessment of inherent immunogenicity, the relative ability of allogeneic and autologous BMDMSCs to stimulate spontaneous proliferation of equine lymphocytes was compared. T...
Journal of proteomicsJanuary 3, 2017
Volume 154 102-108 doi: 10.1016/j.jprot.2016.12.015
Degroote RL, Uhl PB, Amann B, Krackhardt AM, Ueffing M, Hauck SM, Deeg CA.The membrane protein expression repertoire of cells changes in course of activation. In equine recurrent uveitis (ERU), a spontaneous autoimmune disease in horses with relapsing and ultimately blinding inner eye inflammation, CD4+ T lymphocytes are the crucial pathogenic cells activated in the periphery directly prior to an inflammatory episode. In order to find relevant changes in the membrane proteome associated to disease, we sorted CD4+ lymphocytes and compared protein abundance from the generated proteome datasets of both healthy horses and ERU cases. We detected formin like 1, a key play...
Meichner K, Kraszeski BH, Durrant JR, Grindem CB, Breuhaus BA, Moore PF, Neel JA, Linder KE, Borst LB, Fogle JE, Tarigo JL.An 11-year-old, 443-kg Haflinger mare was presented to the North Carolina State University Veterinary Teaching Hospital with a 2-week history of lethargy and a 3-day duration of anorexia, pyrexia, tachycardia, and ventral edema. Severe pitting edema, peripheral lymphadenopathy, and a caudal abdominal mass were noted on physical examination. An extreme leukocytosis (154.3 × 103 /μL) and microscopic hematologic findings suggestive of myelomonocytic leukemia were observed. Serum protein electrophoresis revealed a monoclonal gammopathy and urine protein electrophoresis revealed a monoclonal ligh...
Sarkar S, Bailey E, Go YY, Cook RF, Kalbfleisch T, Eberth J, Chelvarajan RL, Shuck KM, Artiushin S, Timoney PJ, Balasuriya UB.Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10-70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s) of CD3+ T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. ...
Grau-Roma L, Peckham R, Paton J, Stahel A, de Brot S.The postmortem examination of a 14-y-old Appaloosa gelding with clinically diagnosed pituitary pars intermedia dysfunction showed a unique finding of moderate multifocal lymphocytic hypophysitis (LH). The pituitary glands of 24 horses submitted for postmortem examination were examined grossly and examined histologically for the presence of lymphocytes. Of these 23 horses, 1 additional case suffered from moderate LH. The 2 cases with LH tested negative for Equid herpesvirus 1 and 4 by polymerase chain reaction and immunohistochemistry (IHC), and no viral particles were observed by electron micr...
Ziegler A, Everett H, Hamza E, Garbani M, Gerber V, Marti E, Steinbach F.Dendritic cells are professional antigen-presenting cells that play an essential role in the initiation and modulation of T cell responses. They have been studied widely for their potential clinical applications, but for clinical use to be successful, alternatives to xenogeneic substances like fetal bovine serum (FBS) in cell culture need to be found. Protocols for the generation of dendritic cells ex vivo from monocytes are well established for several species, including horses. Currently, the gold standard protocol for generating dendritic cells from monocytes across various species relies u...
Kleinwort KJ, Amann B, Hauck SM, Feederle R, Sekundo W, Deeg CA.Recently, formation of tertiary lymphoid structures was demonstrated and further characterized in the R161H mouse model of spontaneous autoimmune uveitis. In the horse model of spontaneous recurrent uveitis, intraocular lymphoid follicle formation is highly characteristic, and found in all stages and scores of disease, but in depth analyses of immunologic features of these structures are lacking to date. Paraffin-embedded eye sections of cases with equine spontaneous recurrent uveitis (ERU) were characterized with immunohistochemistry to gain insight into the distribution, localization, and si...
BMC research notesJuly 19, 2016
Volume 9 353 doi: 10.1186/s13104-016-2161-9
Tarlinton RE, Alder L, Moreton J, Maboni G, Emes RD, Tötemeyer S.Toll like receptors are one of the major innate immune system pathogen recognition systems. There is little data on the expression of the TLR10 member of this family in the horse. Results: This paper describes the genetic structure of the Equine TLR10 gene and its RNA expression in a range of horse tissues. It describes the phylogenetic analysis of the Equine TLR1,6,10,2 annotations in the horse genome, firmly identifying them in their corresponding gene clades compared to other species and firmly placing the horse gene with other TLR10 genes from odd-toed ungulates. Additional 3' transcript e...
Geisshüsler H, Marti E, Stoffel MH, Kühni K, Stojiljkovic A, von Tscharner C, Vidondo B, Gerber V, Koch C.Sarcoids are the most frequently observed skin tumours in equids and consist of cutaneous accumulations of transformed fibroblasts. Their aetiopathogenesis is closely linked to a presumably abortive infection by bovine papillomavirus (BPV) types 1 and 2. In cattle, dermal fibropapillomas induced by BPV1/2 usually regress spontaneously due to a local, cell-mediated, immune response; however, equids appear to lack an effective immune response to BPV1/2 and mechanisms of immune evasion have been postulated. As a consequence, equine sarcoids tend to persist and are prone to recur. In this study, c...
Durward-Akhurst SA, Finno CJ, Barnes N, Shivers J, Guo LT, Shelton GD, Valberg SJ.Major histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune-mediated myositis (IMM) of humans and dogs and in dysferlin-deficient muscular dystrophy. Objective: To determine if sarcolemmal MHC is expressed in active IMM in horses, if MHC expression is associated with lymphocytic subtype, and if dysferlin is expressed in IMM. Methods: Twenty-one IMM horses of Quarter Horse-related breeds, 3 healthy and 6 disease controls (3 pasture myopathy, 3 amylase-resistant polysaccharide storage myopathy [PSSM]). ...
Simeonova GP, Krastev SZ, Simeonov RS.The pathogenic mechanism of equine recurrent uveitis (ERU) is still poorly defined and many variations between experimental animal models and spontaneous disease exist. Objective: The aim of our study was to investigate if Th17 cell-mediated response plays role in the pathogenesis of the used experimental model in horses and to reveal its pathological findings. Methods: Experimental uveitis was induced in 6 healthy horses. The concentrations of retinal autoantigen CRALBP and IL-17 were measured using ELISA in aqueous humor and vitreous body of the 12 inflamed eyes as well as in 12 control non-...
Wilson AD, Hicks C.Bovine papillomavirus (BPV) infections of equine species have a central role in the aetiology of equine sarcoids; a common benign skin tumour of horses, zebras and donkeys. Within the lesions, all of the early papillomavirus genes are expressed and promote the excessive replication of fibroblasts which characterise these tumours. Equine sarcoids differ from BPV induced fibro-papillomas of cattle (the natural host of BPV), in that they do not produce high amounts of virus particles, do not usually regress spontaneously and do not sero-convert to BPV; features which suggest that affected horses ...
Clark KC, Kol A, Shahbenderian S, Granick JL, Walker NJ, Borjesson DL.Mesenchymal stem cell (MSC) therapy is being increasingly used to treat dogs and horses with naturally-occurring diseases. However these animals also serve as critical large animal models for ongoing translation of cell therapy products to the human market. MSC manufacture for clinical use mandates improvement in cell culture systems to meet demands for higher MSC numbers and removal of xeno-proteins (i.e. fetal bovine serum, FBS). While serum-free media (SFM) is commercially available, its affects on MSC phenotype and immunomodulatory functions are not fully known. The objective of this study...
Witkowski L, Cywinska A, Paschalis-Trela K, Crisman M, Kita J.Equine recurrent uveitis (ERU) has various etiologies, with Leptospira infection and genetic predisposition being the leading risk factors. Regardless of etiology, expression of ocular proteins associated with maintenance of the blood-ocular barrier is impaired in ERU. The recurring-remitting cycle of ERU repeatedly disrupts the blood-ocular barrier, allowing the previously immune-privileged ocular environment to become the site of a progressive local autoimmune pathology that ultimately results in tissue destruction and vision loss. The immune-mediated process involves humoral and cellular me...
Behrens NE, Gershwin LJ.Hypersensitivity reactions, such as hives or fatal anaphylactic shock, in response to vaccination constitute a health hazard for horses that develop allergies to vaccine components. In such horses vaccination with viral vaccines stimulates an IgE response to non-target antigens. Viral vaccines share contaminating non-target proteins, such as bovine serum albumin (BSA); these antigens can stimulate IgE production with each exposure. We hypothesized that the addition of a CpG oligodeoxynucleotide (ODN) administered in conjunction with a West Nile virus vaccine would decrease the IgE response; th...
Bergmann T, Moore C, Sidney J, Miller D, Tallmadge R, Harman RM, Oseroff C, Wriston A, Shabanowitz J, Hunt DF, Osterrieder N, Peters B, Antczak DF....Here we describe a detailed quantitative peptide-binding motif for the common equine leukocyte antigen (ELA) class I allele Eqca-1*00101, present in roughly 25 % of Thoroughbred horses. We determined a preliminary binding motif by sequencing endogenously bound ligands. Subsequently, a positional scanning combinatorial library (PSCL) was used to further characterize binding specificity and derive a quantitative motif involving aspartic acid in position 2 and hydrophobic residues at the C-terminus. Using this motif, we selected and tested 9- and 10-mer peptides derived from the equine herpesvir...
Meulenbroeks C, van der Meide NM, Willemse T, Rutten VP, Tijhaar E.Ponies may suffer from Insect bite hypersensitivity (IBH), an allergic IgE-mediated pruritic skin disorder, induced by allergens from biting midges of the Culicoides spp. Objective: To determine whether recombinant Culicoides obsoletus allergens are able to activate T cells of ponies exposed to C. obsoletus and whether these allergen-specific responses differ between IBH-affected and healthy ponies. Methods: Ten IBH-affected Shetland ponies and 10 age-matched healthy controls taken from the same stables, to ensure similar exposure to midges. Methods: Peripheral blood mononuclear cells (PBMC) w...
Pretorius A, Faber FE, van Kleef M.Development of African horsesickness (AHS) subunit vaccines will have to include a rational approach that uses knowledge of how the virus interacts with the host immune system. The global in vivo immune response induced by attenuated AHSV serotype 4 in horses was characterised using transcriptome sequencing. PBMC were collected with 24h intervals for four days after inoculation and four days after a second boost, 21 days later. Transcriptome data were normalised to the day 0 naïve transcriptome and up- or down-regulated immune genes identified using the CLC workbench. Peak expression was obse...
Olofsson KM, Hjertner B, Fossum C, Press CM, Lindberg R.Inflammatory bowel disease (IBD) in horses is an idiopathic disorder, encompassing different types of chronic intestinal inflammation. The pathogenesis of the disease remains to be established, but it has been suggested that an imbalance between regulatory T cells (Tregs) and T helper 17 (Th17)-associated cytokines and altered toll-like receptor 4 (TLR4) expression is associated with intestinal inflammation in other species. The aim of the present study was to quantify Tregs in rectal biopsies from horses affected with IBD by immunohistochemistry and to evaluate expression of genes encoding in...
Schnabel CL, Steinig P, Koy M, Schuberth HJ, Juhls C, Oswald D, Wittig B, Willenbrock S, Murua Escobar H, Pfarrer C, Wagner B, Jaehnig P, Moritz A....Deoxyribonucleic acid (DNA) vaccines are used for experimental immunotherapy of equine melanoma. The injection of complexed linear DNA encoding interleukin (IL)-12/IL-18 induced partial tumour remission in a clinical study including 27 grey horses. To date, the detailed mechanism of the anti-tumour effect of this treatment is unknown. Results: In the present study, the clinical and cellular responses of 24 healthy horses were monitored over 72 h after simultaneous intradermal and intramuscular application of equine IL-12/IL-18 DNA (complexed with a transfection reagent) or comparative substanc...
Kol A, Wood JA, Carrade Holt DD, Gillette JA, Bohannon-Worsley LK, Puchalski SM, Walker NJ, Clark KC, Watson JL, Borjesson DL.Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses. Methods: We injected three doses of 25 × 10(6) allogeneic MSCs fro...
Hamza E, Mirkovitch J, Steinbach F, Marti E.The immune system of mammals is subject to continuous development during the postnatal phase of life. Studies following the longitudinal development of the immune system in healthy children are limited both by ethical considerations and sample volumes. Horses represent a particular valuable large animal model for T regulatory (Treg) cells and allergy research. We have recently characterised Treg cells from horses, demonstrated their regulatory capability and showed both their expansion and induction in vitro. Insect bite hypersensitivity (IBH) is a common allergy in horses resembling atopic de...
Drbalova J, Musilova P, Kubickova S, Sebestova H, Vahala J, Rubes J.The T cell receptor (TCR) genes (TRA, TRB, TRD and TRG) reside in 3 different chromosomal regions. During the maturation of T lymphocytes, the TCR genes are rearranged by site-specific recombination, a process that also predisposes T cells to aberrant rearrangements. Illegitimate recombination between the TCR genes occurs at a low level in healthy individuals, but this frequency may correlate with the risk of lymphoma. The aim of this work was to investigate interlocus recombination in equids. Illegitimate rearrangements were studied in peripheral blood lymphocytes by FISH with painting and BA...
Ortved K, Wagner B, Calcedo R, Wilson J, Schaefer D, Nixon A.Intraarticular (IA) administration of viral vectors expressing a therapeutic transgene is an attractive treatment modality for osteoarthritis (OA) as the joint can be treated as a contained unit. Humoral and cell-mediated immune responses in vivo can limit vector effectiveness. Transduction of articular tissues has been investigated; however, the immune response to IA vectors remains largely unknown. We hypothesized that IA rAAV2 and rAAV5 overexpressing insulin-like growth factor-I (IGF-I) would result in long-term IGF-I formation but would also induce neutralizing antibodies (NAb) and anti-c...
Aguiar C, Theoret C, Smith O, Segura M, Lemire P, Smith LC.Induced pluripotent stem cells (iPSC) have brought immense hope to cellular therapy and regenerative medicine. However, the antigenicity of iPSC has not been well documented and remains a hurdle for clinical applications. Expression of major histocompatibility complex (MHC) molecules by human and murine iPSC is downregulated, making these cells potentially safe for transplantation. No such data are available for any large animal model. Objective: To measure expression of MHC molecules on equine iPSC (eiPSC) and describe their antigenicity using intradermal testing. The hypothesis was that allo...
Uhl PB, Amann B, Hauck SM, Deeg CA.Retinal pigment epithelium (RPE) builds the outer blood-retinal barrier of the eye. Since one typical feature of the autoimmune disease, equine recurrent uveitis (ERU), is the breakdown of this barrier, we recently performed comparative analysis of healthy and uveitic RPE. We identified for the first time peripherin 2, which is responsible for visual perception and retina development, to be localized in RPE. The purpose of this study was therefore to validate our findings by characterizing the expression patterns of peripherin 2 in RPE and retina. We also investigated whether peripherin 2 expr...
Perkins GA, Wagner B.The development of equine immunity from the fetus to adulthood is complex. The foal's immune response and the immune mechanisms that they are equipped with, along with changes over the first months of life until the immune system becomes adult-like, are only partially understood. While several innate immune responses seem to be fully functional from birth, the onset of adaptive immune response is delayed. For some adaptive immune parameters, such as immunoglobin (Ig)G1, IgG3, IgG5 and IgA antibodies, the immune response starts before or at birth and matures within 3 months of life. Other antib...
Miller CA, Durham AC, Schaffer PA, Ehrhart EJ, Powers BE, Duncan CG.Equine cutaneous lymphoma is an uncommon disease that can present with variable clinical signs, immunosuppression, and rapid systemic disease progression. Various subtypes of equine lymphoma have been described and classified according to a veterinary adaptation of the World Health Organization classification system, but little data is available regarding the association between lymphoma subtypes and epidemiological criteria and/or clinical outcome. The objective of the current study was to classify previously diagnosed cases of equine cutaneous lymphoma and correlate subtypes with clinical da...
Glikin GC, Finocchiaro LM.Despite the important progress obtained in the treatment of some pets' malignancies, new treatments need to be developed. Being critical in cancer control and progression, the immune system's appropriate modulation may provide effective therapeutic options. In this review we summarize the outcomes of published immunogene therapy veterinary clinical trials reported by many research centers. A variety of tumors such as canine melanoma, soft tissue sarcomas, osteosarcoma and lymphoma, feline fibrosarcoma, and equine melanoma were subjected to different treatment approaches. Both viral and mainly ...
Paillot R, Prowse L.The humoral immune response induced by ISCOM-matrix (Immuno Stimulating COMplex-Matrix)-adjuvanted equine influenza virus (EIV) vaccine is well documented in horses. ISCOM-matrix adjuvanted vaccines against human influenza are strong inducers of cell-mediated immunity (CMI), including T cell proliferation and virus-specific cytotoxic T cell. In the horse, the CMI response to equine influenza vaccination is less well characterised. An ISCOM-based vaccine has been shown to induce interferon gamma (IFN-γ) synthesis, a CMI marker, in the horse, but this has not been shown for the ISCOM-matrix vac...
Kelley LC, Mahaffey EA.Gross lesions, microscopic appearance, and immunophenotyping are reported in a retrospective study of 31 cases of equine malignant lymphoma. Immunohistochemical studies were performed on archived formalin-fixed, paraffin-embedded tissues. Monoclonal antibodies to surface glycoprotein BLA.36 and intracytoplasmic domains of mb-1 and B29 were used to document the presence of B lymphocytes in the equine tumors. Polyclonal antibody to CD3 and monoclonal antibodies to T-lymphocyte markers CD3 and CD5 revealed the presence of variable numbers of T cells within the equine lymphomas. The neoplastic com...
McGuire TC, Leib SR, Lonning SM, Zhang W, Byrne KM, Mealey RH.Efficacious lentiviral vaccines designed to induce cytotoxic T lymphocytes (CTL) in outbred populations with a diverse repertoire of MHC class I molecules should contain or express multiple viral proteins. To determine the equine infectious anaemia virus (EIAV) proteins with epitopes most frequently recognized by CTL from seven horses infected for 0.5 to 7 years, retroviral vector-transduced target cells expressing viral proteins were used in CTL assays. Gag p15 was recognized by CTL from 100% of these infected horses. p26 was recognized by CTL from 86%, SU and the middle third of Pol protein ...
Sun Y, Liu Z, Ren L, Wei Z, Wang P, Li N, Zhao Y.This review focuses on the diversity of immunoglobulin (Ig) genes and Ig isotypes that are expressed in domestic animals. Four livestock species-cattle, sheep, pigs, and horses-express a full range of Ig heavy chains (IgHs), including μ, δ, γ, ϵ, and α. Two poultry species (chickens and ducks) express three IgH isotypes, μ, υ, and α, but not δ. The κ and λ light chains are both utilized in the four livestock species, but only the λ chain is expressed in poultry. V(D)J recombination, somatic hypermutation (SHM), and gene conversion (GC) are three distinct mechanisms by which immunog...
Giguère S, Polkes AC.Foals live in an environment heavily populated by bacteria, many of which are capable of causing disease. Development of infection,however, is the exception rather than the rule. The ability of the foal to prevent infection by most pathogens is the result of a sophisticated set of defense mechanisms. These defense mechanisms can be divided into adaptive and innate immunity. Innate immunity encompasses defense mechanisms that pre-exist or are rapidly induced within hours of exposure to a pathogen. Conversely, adaptive or acquired immunity represents host defenses mediated by T and B lymphocytes...
Kleinwort KJ, Amann B, Hauck SM, Feederle R, Sekundo W, Deeg CA.Recently, formation of tertiary lymphoid structures was demonstrated and further characterized in the R161H mouse model of spontaneous autoimmune uveitis. In the horse model of spontaneous recurrent uveitis, intraocular lymphoid follicle formation is highly characteristic, and found in all stages and scores of disease, but in depth analyses of immunologic features of these structures are lacking to date. Paraffin-embedded eye sections of cases with equine spontaneous recurrent uveitis (ERU) were characterized with immunohistochemistry to gain insight into the distribution, localization, and si...
Van Cleemput J, Poelaert KCK, Laval K, Nauwynck HJ.Equine herpesvirus type 5 (EHV5) is a ubiquitous, yet obscure pathogen in the horse population and is commonly associated with fatal equine multinodular pulmonary fibrosis (EMPF). To date, little is known about the precise pathogenesis of EHV5. Here, we evaluated the dynamics of EHV5 infection in representative ex vivo and in vitro equine models, using immunofluorescence staining and virus titration. EHV5 was unable to infect epithelial cells lining the mucosa of nasal and tracheal explants. Similarly, primary equine respiratory epithelial cells (EREC) were not susceptible to EHV5 following in...
Olofsson KM, Hjertner B, Fossum C, Press CM, Lindberg R.Inflammatory bowel disease (IBD) in horses is an idiopathic disorder, encompassing different types of chronic intestinal inflammation. The pathogenesis of the disease remains to be established, but it has been suggested that an imbalance between regulatory T cells (Tregs) and T helper 17 (Th17)-associated cytokines and altered toll-like receptor 4 (TLR4) expression is associated with intestinal inflammation in other species. The aim of the present study was to quantify Tregs in rectal biopsies from horses affected with IBD by immunohistochemistry and to evaluate expression of genes encoding in...
Geburek F, Ohnesorge B, Deegen E, Doeleke R, Hewicker-Trautwein M.We report the historical, clinical and histopathological characteristics of skin lesions in biopsies from 37 heavy draught horses with chronic pastern dermatitis. The skin lesions were divided into four macroscopic groups: scaling (group I, n=5), hyperkeratotic and hyperplastic plaque-like lesions (group II, n=14), nodular skin masses (group III, n=16) and verrucous skin lesions (group IV, n=2). The principal histological findings were hyperkeratosis and epidermal hyperplasia. There was a gradual increase in epidermal hyperplasia from groups I to IV, suggesting that the lesions represent diffe...
Tagmyer TL, Craigo JK, Cook SJ, Issel CJ, Montelaro RC.Equine infectious anemia virus (EIAV) infection of horses provides a valuable model for examining the natural immunological control of lentivirus infection and disease and the mechanisms of protective and enhancing vaccine immunity. We have previously hypothesized that the EIAV envelope (Env) proteins gp90 and gp45 are major determinants of vaccine efficacy, and that the development of protective immunity by attenuated viral vaccines may be associated with the progressive redirection of immune responses from immunodominant, variable Env segments to immunorecessive, conserved Env sequences. Whi...
Tumas DB, Brassfield AL, Travenor AS, Hines MT, Davis WC, McGuire TC.Murine monoclonal antibodies, HB88A, B29A and DH59B separately identify the CD2 T lymphocyte molecule, a unique pan-B lymphocyte surface marker and a pan-granulocyte/monocyte surface molecule, respectively, in the horse. Specificity was shown by two-color immunofluorescent flow cytometry and immunofluorescent microscopy. MAb HB88A reacted with a 52 kDa pan-T lymphocyte molecule present on 75% +/- 7 of peripheral blood lymphocytes (PBL) (n = 15 horses). It also reacted with lymphocytes restricted to T lymphocyte dependent areas of lymph node and spleen. Specificity of mAb HB88A to CD2 was demon...
Chung C, Mealey RH, McGuire TC.Cytotoxic T lymphocytes (CTL) are important for controlling equine infectious anemia virus (EIAV). Because Gag matrix (MA) and capsid (CA) are the most frequently recognized proteins, the hypothesis that CTL from EIAV-infected horses with diverse MHC class I alleles recognize epitope clusters (EC) in these proteins was tested. Four EC were identified by CTL from 15 horses and 8 of these horses had diverse MHC class I alleles. Two of the eight had CTL to EC1, six to EC2, five to EC3, and four to EC4. Because EC2-4 were recognized by CTL from >50% of horses with diverse alleles, the hypothesi...
Mealey RH, Lee JH, Leib SR, Littke MH, McGuire TC.Although CTL are critical for control of lentiviruses, including equine infectious anemia virus, relatively little is known regarding the MHC class I molecules that present important epitopes to equine infectious anemia virus-specific CTL. The equine class I molecule 7-6 is associated with the equine leukocyte Ag (ELA)-A1 haplotype and presents the Env-RW12 and Gag-GW12 CTL epitopes. Some ELA-A1 target cells present both epitopes, whereas others are not recognized by Gag-GW12-specific CTL, suggesting that the ELA-A1 haplotype comprises functionally distinct alleles. The Rev-QW11 CTL epitope is...
Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Couck L, Van den Broeck W, Azab W, Nauwynck HJ.Equine herpesvirus 1 (EHV1) replicates in the respiratory epithelium and disseminates through the body via a cell-associated viremia in leukocytes, despite the presence of neutralizing antibodies. "Hijacked" leukocytes, previously identified as monocytic cells and T lymphocytes, transmit EHV1 to endothelial cells of the endometrium or central nervous system, causing reproductive (abortigenic variants) or neurological (neurological variants) disorders. In the present study, we questioned the potential route of EHV1 infection of T lymphocytes and how EHV1 misuses T lymphocytes as a vehicle to re...
Hamza E, Steinbach F, Marti E.Insect bite hypersensitivity (IBH) is an IgE-mediated dermatitis caused by bites of midges from the genus Culicoides. We have shown previously that peripheral blood mononuclear cells (PBMC) from IBH-affected horses produce higher levels of IL-4 and lower levels of IL-10 and TGF-β1 than those from healthy horses, suggesting that IBH is associated with a reduced regulatory immune response. FoxP3 is a crucial marker of regulatory T cells (Tregs). Here we have determined the proportion of CD4(+)CD25(+)FoxP3(+) T cells by flow cytometry in PBMC directly after isolation or after stimulation with Cu...
Ryan C, Giguère S.The objectives of this study were to compare relative vaccine-specific serum immunoglobulin concentrations, vaccine-specific lymphoproliferative responses, and cytokine profiles of proliferating lymphocytes between 3-day-old foals, 3-month-old foals, and adult horses after vaccination with a killed adjuvanted vaccine. Horses were vaccinated intramuscularly twice at 3-week intervals with a vaccine containing antigens from bovine viral respiratory pathogens to avoid interference from maternal antibody. Both groups of foals and adult horses responded to the vaccine with a significant increase in ...
Williams JH, van Niekerk S, Human S, van Wilpe E, Venter M.Since 2007, West Nile virus (WNV) has been reported in South African horses, causing severe neurological signs. All cases were of lineage 2, except for one case that clustered with lineage 1 viruses. In the present study, gross and microscopic lesions of six South African lineage 2-infected horses and the one lineage 1 case are described. Diagnoses were confirmed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) of central nervous system (CNS) tissue and one by RT-PCR of a brain virus isolate. The CNS of all cases was negative by RT-PCR or immunohistochemistry (IHC) for Afr...
Go YY, Cook RF, Fulgêncio JQ, Campos JR, Henney P, Timoney PJ, Horohov DW, Balasuriya UB.In a recent study, we demonstrated that the virulent Bucyrus strain (VBS) of EAV could infect in vitro a small population of CD3(+) T lymphocytes from some but not all horses. Furthermore, we have shown that a common haplotype is associated with this in vitro CD3(+) T cell susceptibility/resistance phenotype to EAV infection. In this study, we investigated whether the differences in the susceptibility or resistance of CD3(+) T cells in vitro correlate with the outcome and severity of clinical signs in vivo. Thus, horses were divided into two groups based on their CD3(+) T cell susceptible or r...
Soboll G, Hussey SB, Whalley JM, Allen GP, Koen MT, Santucci N, Fraser DG, Macklin MD, Swain WF, Lunn DP.Equine herpesvirus-1 (EHV-1) is the cause of serious disease with high economic impact on the horse industry, as outbreaks of EHV-1 disease occur every year despite the frequent use of vaccines. Cytotoxic T-lymphocytes (CTLs) are important for protection from primary and reactivating latent EHV-1 infection. DNA vaccination is a powerful technique for stimulating CTLs, and the aim of this study was to assess antibody and cellular immune responses and protection resulting from DNA vaccination of ponies with combinations of EHV-1 genes. Fifteen ponies were divided into three groups of five ponies...
Cameron AD, Even KM, Linardi RL, Berglund AK, Schnabel LV, Engiles JB, Ortved KF.Joint injury can cause posttraumatic inflammation, which if severe enough can lead to posttraumatic osteoarthritis (PTOA), a progressive and debilitating condition. Posttraumatic inflammation is characterized by an influx of T lymphocytes and upregulation of inflammatory cytokines and degradative enzymes by activated chondrocytes and synoviocytes. Intra-articular bone marrow-derived mesenchymal stem cell (BM-MSC) injection for the treatment of osteoarthritis (OA) has been of interest due to the immunomodulatory properties of these cells. Interleukin (IL)-10, a potent immunomodulatory cytokine,...
Caplazi P, Ehrensperger F.Borna disease (BD) has been recognized as a virally induced T-cell dependent immunopathological disorder of the central nervous system (CNS), as shown by experimental infection of rats with Borna disease virus (BDV). In contrast to the rat model, little is known about the pathogenesis of spontaneous BD in sheep and horses. The present study describes the brain lesions of 12 ovine and 11 equine cases of naturally occurring BD. A set of monoclonal and polyclonal antibodies was used in order to determine the cells operative in encephalitic lesions and to detect expression of MHC-I and MHC-II prod...
Mekuria ZH, El-Hage C, Ficorilli NP, Washington EA, Gilkerson JR, Hartley CA.Equine herpesvirus 5 (EHV5) is a commonly detected gammaherpesvirus, which, along with the closely related EHV2, constitute the only two known percaviruses that infect horses. Apart from detection in horse populations worldwide and the recent publication of the whole genome, there is little known about the biology and pathogenesis of this virus, with many assumptions made by parallels with EHV2. The long-term survival of gammaherpesviruses within infected hosts involves the establishment and maintenance of latency in selected cell and tissues types, particularly lymphocytes. A latent gammaherp...
Goodman LB, Wimer C, Dubovi EJ, Gold C, Wagner B.Equine herpesvirus 1 (EHV-1) induces a variety of disease manifestations, including respiratory disease, abortions, and myeloencephalopathy. Several vaccines are commercially available but could not previously be distinguished by serologic testing from infection with EHV-1 (or the closely related EHV-4). Currently available vaccines are not reliably protective against the severe manifestations of the disease, including fatal myeloencephalopathy. We determined immunological parameters that can differentiate vaccinated from previously infected animals by comparing humoral and cellular EHV-1-spec...
Kakhniashvili I, Filicko J, Kraft WK, Flomenberg N.Antithymocyte globulins (ATG) are purified, concentrated preparations of polyclonal immunoglobulin G from hyperimmune serum of horses or rabbits immunized with human thymus lymphocytes. Both the horse and the rabbit products induce immunosuppression as a result of lymphocyte depletion and immune modulation. The exact mechanism of action is unknown but may include T-cell clearance from the circulation and modulation of T-cell activation, homing, and cytotoxic activities. Both horse and rabbit ATG include multiple antibodies against T-cell surface antigens and have been used extensively in allog...
Furrer E, Bilzer T, Stitz L, Planz O.Experimental Borna disease virus (BDV) infection of rats and natural infection of horses and sheep leads to severe central nervous system disease based on immunopathological pathways. The virus replicates slowly, and the cellular immune response results in immunopathology. CD8(+) T cells exert effector cell functions, and their activity results in the destruction of virus-infected cells. Previously, Oldach and colleagues (D. Oldach, M. C. Zink, J. M. Pyper, S. Herzog, R. Rott, O. Narayan, and J. E. Clements, Virology 206:426-434, 1995) have reported protection against Borna disease after inocu...
Grünig G, Triplett L, Canady LK, Allen WR, Antczak DF.Invading trophoblasts form endometrial cups in the endometrium of the pregnant mare. In the present study we characterized the maternal leucocyte response to endometrial cups from their formation to their regression. The maternal leucocyte response was correlated with the stages of trophoblast development. (1) Aggregates of CD4+ and CD8+ cells were present between the migrating and differentiating endometrial cup trophoblasts and surrounding the forming endometrial cups. (2) Numbers of CD4+ cells within the mature endometrial cups were much reduced. At the periphery of the endometrial cups CD4...
Lunn DP, Holmes MA, Duffus WP.The aim of this study was to produce monoclonal antibodies (mAb) recognizing equine lymphocyte surface antigens. Fusions were conducted using BALB/c mice hyperimmunized with equine thymocytes. Hybridoma supernatants were screened by flow cytometry and positive hybridomas were cloned twice by limiting dilution. These mAb were then characterized for tissue distribution by immunohistology and flow cytometry, and by precipitation and analysis of the lymphocyte antigens which they recognized. Three mAb (CVS5, CVS4 and CVS8) are described which recognize only T lymphocytes in peripheral blood. Two-c...
Futas J, Horin P.Natural killer (NK) cells have important functions in immunity. NK recognition in mammals can be mediated through killer cell immunoglobulin-like receptors (KIR) and/or killer cell lectin-like Ly49 receptors. Genes encoding highly variable NK cell receptors (NKR) represent rapidly evolving genomic regions. No single conservative model of NKR genes was observed in mammals. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species. In contrast to other non-rodent mammals, multiple Ly49-like genes appear to exist ...
Tomlinson JE, Wolfisberg R, Fahnøe U, Patel RS, Trivedi S, Kumar A, Sharma H, Nielsen L, McDonough SP, Bukh J, Tennant BC, Kapoor A, Rosenberg BR....Equine hepacivirus (EqHV) is phylogenetically the closest relative of HCV and shares genome organization, hepatotropism, transient or persistent infection outcome, and the ability to cause hepatitis. Thus, EqHV studies are important to understand equine liver disease and further as an outbred surrogate animal model for HCV pathogenesis and protective immune responses. Here, we aimed to characterize the course of EqHV infection and associated protective immune responses. Seven horses were experimentally inoculated with EqHV, monitored for 6 months, and rechallenged with the same and, subsequen...
