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.
Rodríguez M, Quiroga J, Cortés B, Morán G, Henríquez C.Tamoxifen (TAM) is widely utilized in the prevention and treatment of human breast cancer and has demonstrated the potential to modulate the immune response. It has been proposed as a therapeutic tool for immune-mediated diseases. TAM has been investigated as a possible treatment for asthma-like conditions in horses, revealing specific impacts on the innate immune system. While the effects of TAM on equine neutrophils are well-documented, its influence on lymphocytes and the modulation of the immune response polarization remains unclear. This study employed peripheral blood mononuclear cells ...
Terpeluk ER, Schäfer J, Finkler-Schade C, Schuberth HJ.Feed supplements supporting animal welfare and performance are becoming increasingly important. Immunomodulatory effects of such products have been observed in many species. The aim of this study was to analyze whether food supplementation with a fermentation product (SCFP) affects the occurrence of foal diarrhea in early life, and whether the SCFP feeding has an impact on the immediate response to a parenteral vaccination at the age of 6-9 months. Eleven foals received the SCFP (OLI) and eleven foals were fed a placebo (PLA) for 29 days. Growth, diarrhea, and diarrhea severity were observed ...
Sage SE, Leeb T, Jagannathan V, Gerber V.Severe equine asthma (SEA) is a complex respiratory condition characterized by chronic airway inflammation. It shares many clinical and pathological features with human neutrophilic asthma, making it a valuable model for studying this condition. However, the immune mechanisms driving SEA have remained elusive. Although SEA has been primarily associated with a Th2 response, there have also been reports of Th1, Th17, or mixed-mediated responses. To uncover the elusive immune mechanisms driving SEA, we performed single-cell mRNA sequencing (scRNA-seq) on cryopreserved bronchoalveolar cells from 1...
Bourebaba L, Serwotka-Suszczak A, Bourebaba N, Zyzak M, Marycz K.Hyperactivation of protein tyrosine phosphatase (PTP1B) has been associated with several metabolic malfunctions ranging from insulin resistance, metaflammation, lipotoxicity, and hyperglycaemia. Liver metabolism failure has been proposed as a core element in underlying endocrine disorders through persistent inflammation and highly fibrotic phenotype. Unassigned: In this study, the outcomes of PTP1B inhibition using trodusquemine (MSI-1436) on key equine metabolic syndrome (EMS)-related alterations including inflammation, fibrosis, and glucose uptake have been analyzed in liver explants collect...
Hamouzová P, Drábková Z, Stehlíková Š, Řeháková K, Čížek P, Dobešová O, Jahn P, Doubek J.This study determined Tregs and inflammatory cytokines in BALF and peripheral blood (PB) of adult horses with mild and severe asthma and different BALF cytological inflammation profiles. Horses of diverse breeds with asthma (age range: 2-20 years, n = 24) were divided into groups according to the number of points obtained in a standardized clinical scoring system (mild-moderate equine asthma - MEA, severe equine asthma - SEA) and according to the inflammation type based on cytological finding. Plasma levels of IFN-γ, IL-4, IL-10, IL-17 and MMP-9 in the BALF were determined by ELISA. Tregs ...
Loubière C, Moreau P, Marine R, Hélie P, Jean D.The objectives of this study were to quantify lymphocytes and eosinophils in the mucosa of the duodenum and rectum in asthmatic horses. Asthmatic horses were evaluated in a symptomatic (after 6 weeks of exposure to moldy hay) and asymptomatic status (3 and 7 months after being fed alfalfa pellets [n = 4] or treated with inhaled fluticasone [6]). Duodenal and rectal biopsies were endoscopically (n = 4 to 6) taken in each horse. Eosinophils were counted on slides stained with hematoxylin, eosin, phloxine, and saffron, and immunohistochemistry was used to evaluate T and B lymphocytes using CD3 an...
Smith HL, Berglund AK, Robertson JB, Schnabel LV, McMullen RJ, Gilger BC, Oh A.The objective of the study was to determine the effect of gentamicin on CD3+ T-lymphocyte proliferation and cell viability using an in vitro cell culture model as a means of investigating the mechanism of action of low-dose intravitreal gentamicin injection. Methods: Three adult horses with no evidence of ophthalmic or systemic disease. Methods: Peripheral blood lymphocytes were treated with gentamicin at concentrations 37.5 μg/mL, 112.5 μg/mL, 187 μg/mL, 375 μg/mL, or 750 μg/mL then stimulated to proliferate with concanavalin A (ConA). 4',6-diamidino-2-phenylindole (DAPI) and c...
Rissi DR, Avery AC, Burnett RC.T-cell-rich, large B-cell lymphoma (TCRLBCL) is the most commonly diagnosed type of lymphoma in horses. Here we describe the clinical signs, neuropathology, immunohistochemistry (IHC), and PCR for antigen receptor rearrangement (PARR) analysis results of a TCRLBCL in the brain of an 8-y-old male Quarter Horse that was euthanized after acute anorexia, tremors, head pressing, falling, blindness, incoordination, and seizures. Autopsy revealed a firm, smooth, pale-yellow mass that expanded both lateral ventricles and the adjacent subcortical white matter. Histologically, the mass consisted of a de...
Keller LE, Tait Wojno ED, Begum L, Fortier LA.Infiltration of cluster of differentiation (CD) 3 (CD3) T cells into the synovium and synovial fluid occurs in most patients with posttraumatic osteoarthritis. During disease progression, proinflammatory T helper 17 cells and anti-inflammatory regulatory T cells infiltrate the joint in response to inflammation. This study aimed to characterize the dynamics of regulatory T and T helper 17 cell populations in synovial fluid from equine clinical patients with posttraumatic osteoarthritis to determine whether phenotype and function are associated with potential immunotherapeutic targets. An imbala...
Zhao S, Pan F, Cai S, Yi J, Zhou L, Liu Z.This study systematically investigated the differences in allergenicity of casein in cow milk (CM), goat milk (GM), camel milk (CAM), and mare milk (MM) from protein structures using bioinformatics. Primary structure sequence analysis reveals high sequence similarity between the -casein of CM and GM, while all allergenic subtypes are likely to have good hydrophilicity and thermal stability. By analyzing linear B-cell epitope, T-cell epitope, and allergenic peptides, the strongest casein allergenicity is observed for CM, followed by GM, and the casein of MM has the weakest allergenicity. Meanwh...
Jaworska J, de Mestre AM, Wiśniewska J, Wagner B, Nowicki A, Kowalczyk-Zięba I, Wocławek-Potocka I.Endometrial immune cells are essential to support uterine functions across the estrous cycle and in preparation for pregnancy. It has been acknowledged that changes in phenotype and/or numbers of lymphocytes, such as regulatory T cells (Tregs) and NK cells, might result in lower fertility in women and mice. Little is known about equine endometrial immune cells across the estrous cycle. Here, we compared the populations of endometrial Tregs and NK cells in estrus and diestrus in mares. Endometrial biopsy and blood samples were taken in estrus and diestrus from 11 mares ages 4-12 years. Flow cyt...
Wotman KL, Chow L, Martabano B, Pezzanite LM, Dow S.Ocular surface squamous neoplasia (OSSN) is the major cause of corneal cancer in man and horses worldwide, and the prevalence of OSSN is increasing due to greater UVB exposure globally. Currently, there are no approved treatments for OSSN in either species, and most patients are managed with surgical excision or off-label treatment with locally injected interferon alpha, or topically applied cytotoxic drugs such as mitomycin C. A more broadly effective and readily applied immunotherapy could exert a significant impact on management of OSSN worldwide. We therefore evaluated the effectiveness of...
Stefansdottir SB, Jonsdottir S, Kristjansdottir H, Svansson V, Marti E, Torsteinsdottir S.Insect bite hypersensitivity (IBH) is a seasonal dermatitis of horses caused by IgE-mediated reactions to bites of Culicoides midges characterized by an imbalance of T-cell subsets. Iceland is free of the causative species but the prevalence of IBH in exported Icelandic horses is especially high. We have shown that intralymphatic (i.l.) vaccination with r-Culicoides allergens in Aluminum hydroxide (alum) and monophosphoryl lipid A (MPLA) adjuvants induces a desired Th1/regulatory T-cell response. The aim of this study was to compare i.l. to subcutaneous (s.c.) injection. Twelve healthy Iceland...
Faber E, Tshilwane SI, Van Kleef M, Pretorius A.Transcriptome analysis was used to characterise the in vitro primary and secondary immune responses induced in horse peripheral blood mononuclear cells (PBMC) stimulated for 24 h with the individual recombinant proteins of a virulent AHSV serotype 4 (AHSV4) field isolate (rAHSV4 proteins) that were previously expressed in Escherichia coli (E. coli). The results showed that the E. coli contamination products greatly affected the innate and humoral immune response transcripts. Hence, the impact of E. coli contamination products present in the individual rAHSV4 proteins on the translational immu...
Sage SE, Nicholson P, Peters LM, Leeb T, Jagannathan V, Gerber V.The transcriptomic profile of a cell population can now be studied at the cellular level using single-cell mRNA sequencing (scRNA-seq). This novel technique provides the unprecedented opportunity to explore the cellular composition of the bronchoalveolar lavage fluid (BALF) of the horse, a species for which cell type markers are poorly described. Here, scRNA-seq technology was applied to cryopreserved equine BALF cells. Analysis of 4,631 cells isolated from three asthmatic horses in remission identified 16 cell clusters belonging to six major cell types: monocytes/macrophages, T cells, B/plasm...
Even KM, Gaesser AM, Ciamillo SA, Linardi RL, Ortved KF.Joint injury often leads to cartilage damage and posttraumatic inflammation, which drives continued extracellular matrix degradation culminating in osteoarthritis. Mesenchymal stem cells (MSCs) have been proposed as a biotherapeutic to modulate inflammation within the joint. However, concerns have been raised regarding the immunogenicity of MSCs cultured in traditional fetal bovine serum (FBS) containing media, and the potential of xenogenic antigens to activate the immune system causing rejection and destruction of the MSCs. Xenogen-free alternatives to FBS have been proposed to decrease MSC ...
Klier J, Fuchs S, Winter G, Gehlen H.Severe equine asthma is the most common globally widespread non-infectious equine respiratory disease (together with its mild and moderate form), which is associated with exposure to hay dust and mold spores, has certain similarities to human asthma, and continues to represent a therapeutic problem. Immunomodulatory CpG-ODN, bound to gelatin nanoparticles as a drug delivery system, were successfully administered by inhalation to severe equine asthmatic patients in several studies. It was possible to demonstrate a significant, sustained, and allergen-independent one-to-eight-week improvement in...
Kondratjeva J, Julien F, Coutelier C, Humeau L, Moog F, Combarros D, Fourquaux I, Pressanti C, Delverdier M, Moore PF, Cadiergues MC.Cutaneous epitheliotropic T-cell lymphoma is a malignant tumour of the skin already reported in humans, dogs, cats, horses, and other species, but not previously in donkeys. The standard diagnosis is based on clinical, morphological and immunophenotypic data. Differentiation of malignant versus benign proliferation of lymphocytes is crucial; in ambiguous cases T-cell receptor gamma (TRG) molecular clonality should be tested. In the present paper, we report a case of mycosis fungoides diagnosed in a donkey whose diagnosis was based on clinical, histological and immunohistochemical aspects and a...
Birdwhistell KE, Hurley DJ, Heins B, Peroni JF.Allogeneic solid organ transplantation is currently the only treatment option for end stage organ disease. The shortage of available donor organs has driven efforts to utilize xenogeneic organs for transplantation. In vitro methods for evaluating immune-compatibility are a quick and low cost means of screening novel tissue products prior to more involved, expensive, and invasive live animal studies. Recently, a new analog of the DNA base thymidine, 5-ethynyl-2'-deoxyuridine (EdU), was developed. It may be used in a fast, efficient and specific means of evaluating cell proliferation via flow cy...
Schnabel CL, Fletemeyer B, Lübke S, Marti E, Wagner B, Alber G.Despite the relevance of adaptive immunity against equine pathogens antigen-specific T cell responses of horses are not well characterized and the lack of insight into T cell responses hampers the understanding of the pathogeneses of important diseases. In this study we used tetanus toxoid (TT) as a well-defined antigen to characterize antigen-reactive T cells. Six healthy adult horses received a routine booster against tetanus with an immune stimulating complex (ISCOM)-based vaccine and were followed for 28 days. TT-specific serum antibodies were quantified by ELISA and increased in all horse...
Cequier A, Romero A, Vázquez FJ, Vitoria A, Bernad E, Fuente S, Zaragoza P, Rodellar C, Barrachina L.Immunomodulation and immunogenicity are pivotal aspects for the therapeutic use of mesenchymal stem cells (MSCs). Since the horse is highly valuable as both a patient and translational model, further knowledge on equine MSC immune properties is required. This study analysed how inflammation, chondrogenic differentiation and compatibility for the major histocompatibility complex (MHC) influence the MSC immunomodulatory-immunogenicity balance. Equine MSCs in basal conditions, pro-inflammatory primed (MSC-primed) or chondrogenically differentiated (MSC-chondro) were co-cultured with either autolo...
Asakawa MG, Jamieson CA, David F, Johnson JP, Mehmood W, Oikawa MA.A 5-year-old Arabian broodmare with acute colic was diagnosed with lymphocytic ganglioneuritis of the coeliac-mesenteric ganglia and lymphocytic‒plasmacytic enterocolitis resembling inflammatory bowel disease. No significant pathogens were identified by aerobic culture or histopathological examination. The ganglia were multifocally infiltrated with small lymphocytes that were immunopositive for CD3 and negative for CD20 and CD79a antigens, indicating CD3+ T-lymphocyte-mediated coeliac-mesenteric ganglioneuritis. The findings suggest immune-mediated inflammatory bowel disease resulting in dis...
Simões J, Batista M, Tilley P.Severe equine asthma is a chronic respiratory disease of adult horses, occurring when genetically susceptible individuals are exposed to environmental aeroallergens. This results in airway inflammation, mucus accumulation and bronchial constriction. Although several studies aimed at evaluating the genetic and immune pathways associated with the disease, the results reported are inconsistent. Furthermore, the complexity and heterogeneity of this disease bears great similarity to what is described for human asthma. Currently available studies identified two chromosome regions (ECA13 and ECA15) a...
Saini S, Singha H, Shanmugasundaram K, Tripathi BN.Burkholderia mallei causes a highly fatal infectious disease in equines known as glanders. It is one of the OIE listed notifiable diseases, which entails strict control policy measures once B. mallei infection is confirmed in the susceptible hosts. Humans, especially equine handlers, veterinary professionals and laboratory workers are at greater risk to acquire the B. mallei infection directly through prolonged contact with glanderous equines, and indirectly through unprotected handling of B. mallei contaminated materials. Further, natural resistance of B. mallei to multiple antibiotics, aeros...
Kamm JL, Riley CB, Parlane NA, Gee EK, McIlwraith CW.Mesenchymal stromal cells (MSCs) are believed to be hypoimmunogeneic with potential use for allogeneic administration. Bone marrow was harvested from Connemara (n = 1), Standardbred (n = 6), and Thoroughbred (n = 3) horses. MSCs were grouped by their level of expression of major histocompatibility factor II (MHC II). MSCs were then sub-grouped by those MSCs derived from universal blood donor horses. MSCs were isolated and cultured using media containing fetal bovine serum until adequate numbers were acquired. The MSCs were cultured in xenogen-free media for 48 h prior to use and d...
Carroll CSE, Andrew ER, Malik L, Elliott KF, Brennan M, Meyer J, Hintze A, Almonte AA, Lappin C, MacPherson P, Schulte KM, Dahlstrom JE, Tamhane R....We describe intratumoral injection of a slow-release emulsion of killed mycobacteria (complete Freund's adjuvant (CFA)) in three preclinical species and in human cancer patients. Efficacy and safety were tested in mammary tumors in mice, in mastocytomas in mice and dogs, and in equine melanomas. In mice, survival, tumor growth, and tumor infiltration by six immune cell subsets (by flow cytometry) were investigated and analyzed using Cox proportional hazards, a random slopes model, and a full factorial model, respectively. Tumor growth and histology were investigated in dogs and horses, as well...
Hay AN, Potter A, Lindsay D, LeRoith T, Zhu J, Cashwell S, Witonsky S, Leeth C.Sarcocystis neurona is the predominant etiological agent of the infectious equine neurologic disease, equine protozoal myeloencephalitis (EPM), which is prevalent in the United States. A wealth of knowledge about S. neurona biology and its life cycle has accumulated over the last several decades. However, much remains unknown about the aberrant equine host's immune response to S. neurona and the relatively high prevalence of exposure to the protozoa but relatively infrequent occurrence of clinical neurologic disease. Mouse models simulating EPM are commonly used to study the disease due to num...
Fettelschoss-Gabriel A, Birkmann K, Pantelyushin S, Kündig TM.Equine Culicoides hypersensitivity (CH) is the most common allergic condition in horses affecting the skin. This review focuses on immunopathology and molecular mechanisms of equine CH. The role of eosinophils is emphasized, as well as disease severity and the influence of long-term chronic allergen exposure on T helper (Th) 2 cells. Using current knowledge from human allergic disorders, similar effects are hypothesized in equine patients. Key aspects of CH diagnosis and treatment are discussed, focusing on allergen specific immunotherapy and allergen-independent approaches, such as targeting ...
Keller LE, Tait Wojno ED, Begum L, Fortier LA.To gain insight into Treg interactions with synovial tissues in early OA, an equine tri-culture model of OA was used to test the hypothesis that Tregs, in the absence of T Helper 17 cells, are sufficient to resolve inflammation elicited by IL-1β. Unassigned: To model normal and OA joints, synoviocytes were co-cultured with chondrocytes in a transwell system and ± stimulated with IL-1β. Tregs were activated and enriched, then added to co-cultures, creating tri-cultures. At culture end, synoviocytes and chondrocytes were analyzed for gene expression, Treg Foxp3 expression was reexamined b...
Carrade DD, Lame MW, Kent MS, Clark KC, Walker NJ, Borjesson DL.Mesenchymal stem cells (MSCs) derived from bone marrow (BM), adipose tissue (AT), umbilical cord blood (CB), and umbilical cord tissue (CT) are increasingly being used to treat equine inflammatory and degenerative lesions. MSCs modulate the immune system in part through mediator secretion. Animal species and MSC tissue of origin are both important determinants of MSC function. In spite of widespread clinical use, how equine MSCs function to heal tissues is fully unknown. In this study, MSCs derived from BM, AT, CB, and CT were compared for their ability to inhibit lymphocyte proliferation and ...
Hammond SA, Cook SJ, Lichtenstein DL, Issel CJ, Montelaro RC.Equine infectious anemia virus (EIAV) provides a natural model system by which immunological control of lentivirus infections may be studied. To date, no detailed study addressing in parallel both the humoral and cellular immune responses induced in horses upon infection by EIAV has been conducted. Therefore, we initiated the first comprehensive characterization of the cellular and humoral immune responses during clinical progression from chronic disease to inapparent stages of EIAV infection. Using new analyses of antibody avidity and antibody epitope conformation dependence that had not been...
Carrade Holt DD, Wood JA, Granick JL, Walker NJ, Clark KC, Borjesson DL.Mesenchymal stem cells (MSCs) are used in both human clinical trials and veterinary medicine for the treatment of inflammatory and immune-mediated diseases. MSCs modulate inflammation by decreasing the cells and products of the inflammatory response. Stimulated equine MSCs from bone marrow (BM), adipose tissue (AT), cord blood (CB), and umbilical cord tissue (CT) inhibit lymphocyte proliferation and decrease inflammatory cytokine production. We hypothesized that equine MSCs inhibit T cell proliferation through secreted mediators and that MSCs from different tissue sources decrease T cell proli...
Carrade DD, Affolter VK, Outerbridge CA, Watson JL, Galuppo LD, Buerchler S, Kumar V, Walker NJ, Borjesson DL.BACKGROUND AIMS. The use of allogeneic mesenchymal stem cells (MSC) to treat acute equine lesions would greatly expand equine cellular therapy options; however, the safety and antigenicity of these cells have not been well-studied. We hypothesized that equine allogeneic umbilical cord tissue (UCT)-derived MSC would not elicit acute graft rejection or a delayed-type hypersensitivity response when injected intradermally. METHODS. Six Quarterhorse yearlings received 12 intradermal injections (autologous MSC, allogeneic MSC, positive control and negative control, in triplicate) followed by the sam...
El Garch H, Minke JM, Rehder J, Richard S, Edlund Toulemonde C, Dinic S, Andreoni C, Audonnet JC, Nordgren R, Juillard V.Successful vaccination against West Nile virus (WNV) requires induction of both neutralizing antibodies and cell-mediated immune responses. In this study, we have assessed the ability of a recombinant ALVAC-WNV vaccine (RECOMBITEK WNV) to elicit neutralizing antibodies and virus-specific cell-mediated immune responses in horses. In addition, we examined whether prior exposure to ALVAC-WNV vaccine would inhibit B and cell-mediated immune responses against the transgene product upon subsequent booster immunizations with the same vaccine. The results demonstrated that the recombinant ALVAC-WNV va...
Cassano JM, Schnabel LV, Goodale MB, Fortier LA.Inflammatory licensed mesenchymal stem cells (MSCs) have the ability to promote functional tissue repair. This study specifically sought to understand how the recipient tissue environment reciprocally affects MSC function. Inflammatory polarized macrophages, modeling an injured tissue environment, were exposed to licensed MSCs, and the resultant effects of MSC immunomodulation and functionality of the MSC secretome on chondrocyte homeostasis were studied. Inflammatory licensed MSCs were generated through priming with either IFN-γ or polyinosinic:polycytidylic acid (poly I:C). Macrophages were...
Schaffartzik A, Hamza E, Janda J, Crameri R, Marti E, Rhyner C.Insect bite hypersensitivity (IBH) is an allergic dermatitis of the horse caused by bites of insects of the genus Culicoides and is currently the best characterized allergic disease of horses. This article reviews knowledge of the immunopathogenesis of IBH, with a particular focus on the causative allergens. Whereas so far hardly any research has been done on the role of antigen presenting cells in the pathogenesis of IBH, recent studies suggest that IBH is characterized by an imbalance between a T helper 2 (Th2) and regulatory T cell (T(reg)) immune response, as shown both locally in the skin...
Takahashi T, Yawata M, Raudsepp T, Lear TL, Chowdhary BP, Antczak DF, Kasahara M.In rodents, the Ly49 family encodes natural killer (NK) receptors interacting with classical MHC class I molecules, whereas the corresponding receptors in primates are members of the killer cell immunoglobulin-like receptor (KIR) family. Recent evidence indicates that the cattle, domestic cat, dog, and pig have a single LY49 and multiple KIR genes, suggesting that predominant NK receptors in most non-rodent mammals might be KIR. Here, we show that the horse has at least six LY49 genes, five with an immunoreceptor tyrosine-based inhibition motif (ITIM) and one with arginine in the transmembrane...
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...
Paebst F, Piehler D, Brehm W, Heller S, Schroeck C, Tárnok A, Burk J.Horses are an approved large animal model for therapies of the musculoskeletal system. Especially for tendon disease where cell-based therapy is commonly used in equine patients, the translation of achieved results to human medicine would be a great accomplishment. Immunophenotyping of equine mesenchymal stromal cells (MSCs) remains the last obstacle to meet the criteria of the International Society for Cellular Therapy (ISCT) definition of human MSCs. Therefore, the surface antigen expression of CD 29, CD 44, CD 73, CD 90, CD 105, CD 14, CD 34, CD 45, CD 79α, and MHC II in equine MSCs from a...
Garcia-Tapia D, Loiacono CM, Kleiboeker SB.A cell model of primary monocytes and other mononuclear cells isolated from equine blood was used to study the kinetics of West Nile virus (WNV) replication in a natural host. West Nile virus has emerged on the North American continent as a significant cause of morbidity and mortality in a wide range of avian and mammalian species. While other flaviviruses are known to infect monocytes and lymphocytes, the ability of WNV to productively replicate in specific immune cells of peripheral blood has not been assessed. In this study, enriched populations of monocytes and lymphocytes as well as purif...
Richt JA, Pfeuffer I, Christ M, Frese K, Bechter K, Herzog S.The geographic distribution and host range of Borna disease (BD), a fatal neurologic disease of horses and sheep, are larger than previously thought. The etiologic agent, Borna disease virus (BDV), has been identified as an enveloped nonsegmented negative-strand RNA virus with unique properties of replication. Data indicate a high degree of genetic stability of BDV in its natural host, the horse. Studies in the Lewis rat have shown that BDV replication does not directly influence vital functions; rather, the disease is caused by a virus-induced T-cell mediated immune reaction. Because antibodi...
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...
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...
Kydd J, Antczak DF, Allen WR, Barbis D, Butcher G, Davis W, Duffus WP, Edington N, Grünig G, Holmes MA.The First International Workshop on Equine Leucocyte Antigens was organized and convened for the purposes of identifying immunologically relevant cell surface molecules of equine leucocytes and establishing a system of nomenclature for those molecules. Participating members of the workshop represented the majority of laboratories world-wide engaged in the tasks of production and characterization of equine leucocyte and lymphocyte markers using monoclonal antibodies. The workshop confirmed the identification of several equine CD molecules described previously by individual laboratories, and in ...
de Mestre A, Noronha L, Wagner B, Antczak DF.Split immunological tolerance refers to states in which an individual is capable of mounting certain types of immune responses to a particular antigenic challenge, but is tolerant of the same antigen in other compartments of the immune system. This concept is applicable to the immunological relationship between mother and fetus, and particularly relevant in equine pregnancy. In pregnant mares, antibody responses to paternal foreign Major Histocompatibility Complex class I antigens are robust, while anti-paternal cytotoxic T cell responses are diminished compared to those mounted by non-pregnan...
Deeg CA, Kaspers B, Gerhards H, Thurau SR, Wollanke B, Wildner G.To test the hypothesis that autoimmune mechanisms are involved in horses in which equine recurrent uveitis (ERU) develops spontaneously. Methods: Material obtained from horses treated for spontaneous disease by therapeutic routine vitrectomy was analyzed for total IgG content and IgG specific for S-Antigen (S-Ag) and interphotoreceptor retinoid-binding protein (IRBP). The cellular infiltrate of the vitreous was analyzed by differential counts of cytospin preparations and flow cytometry using equine lymphocyte-specific antibodies. Antigen-specific proliferation assays were performed comparing p...
Mealey RH, Zhang B, Leib SR, Littke MH, McGuire TC.Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data doc...
Kanaly ST, Hines SA, Palmer GH.Rhodococcus equi, a facultative intracellular bacterium, causes chronic, often fatal granulomatous pneumonia in young horses and in humans with AIDS. The inability of host alveolar macrophages to kill intracellular R. equi results in the development of granulomas and progressive loss of pulmonary parenchyma. Clearance of the organism from the lung requires functional CD4+ T cells. The purpose of this study was to identify the cytokine effector mechanisms that mediate clearance of R. equi from the lung. Mice were treated with monoclonal antibodies (MAbs) to either gamma interferon (IFN-gamma) o...
Lopez AM, Hines MT, Palmer GH, Alperin DC, Hines SA.Rhodococcus equi infects and causes pneumonia in foals between 2 and 4 months of age but does not induce disease in immunocompetent adults, which are immune and remain clinically normal upon challenge. Understanding the protective response against R. equi in adult horses is important in the development of vaccine strategies, since those mechanisms likely reflect the protective phenotype that an effective vaccine would generate in the foal. Twelve adult horses were challenged with virulent R. equi and shown to be protected against clinical disease. Stimulation of cells obtained from bronchoalve...
McGuire TC, Poppie MJ, Banks KL.Thirty sick Arabian foals and 78 clinically normal Arabian foals were examined for combined (B- and T-lymphocyte) immunodeficiency. Diagnosis was based on lymphocyte counts and serum immunoglobulin (Ig) content or microscopic examination of lymphoid organs. Ten of the 30 sick foals and 2 of the 78 clinically normal foals had combined immunodeficiency. The 2 affected foals in the group of 78 subsequently developed fatal pneumonia.
Lymphocyte counts were made from 9 of the 12 immunodeficient foals; the range was 0 to 936/cmm., whereas the normal mean was 4,119/cmm., with a standard deviation ...
McGuire TC, Poppie MJ.A severe combined immunodeficiency disorder was demonstrated in two Arabian foals which were full siblings. The defect in the B-lymphocyte system was shown by hypogammaglobulinemia, lymphopenia, and absence of germinal centers. The almost total absence of thymic tissue in one foal and the lack of thymic dependent lymphocytes in the spleens of both foals demonstrate a T-lymphocyte defect. In a retrospective study of total available Arabian foal cases, 4 of 15 had evidence of immunodeficiency.
Paterson YZ, Rash N, Garvican ER, Paillot R, Guest DJ.Autologous mesenchymal stem cells (MSCs) are an attractive concept in regenerative medicine, but their mechanism of action remains poorly defined. No immune response is reported after in vivo injection of allogeneic equine MSCs or embryo-derived stem cells (ESCs) into the equine tendon, which may be due to the cells' immune-privileged properties. This study further investigates these properties to determine their potential for clinical application in other tissues. Methods: Mitomycin C-treated MSCs, ESCs, or differentiated ESCs (dESCs) were cultured with allogeneic equine peripheral blood mono...
Allen G, Yeargan M, Costa LR, Cross R.An experimental system that permits sensitive and reproducible detection of equine herpesvirus 1 (EHV-1)-specific cytotoxic T-lymphocyte (CTL) activity in the horse was developed. Peripheral blood mononuclear cells (PBMC) collected from immune horses were restimulated in vitro by culture with live EHV-1. Cytotoxic activity against virus-infected, pokeweed mitogen-stimulated lymphoblast targets was assessed in a 4-h 51Cr release assay. The optimal conditions for in vitro stimulation of equine memory CTLs and for preparation of EHV-1-infected target cells expressing viral antigens were systemati...
Corradin G, Chiller JM.Murine T-lymphocyte specificity was determined in a system of antigen driven in vitro T-cell proliferation using cytochrome c molecules from different species, their derived peptides and reconstituted hybrid proteins. It was observed that primed T cells could discriminate between peptide fragments which differed from each other at a single amino acid residue. These conclusions were substantiated by the pattern of cross-reactivity noted in the response of closely related cytochrome c proteins as well as when artificial hybrid molecules reconstituted by the covalent linkage of peptide fragments ...
Noronha LE, Antczak DF.The horse has proven to be a distinctively informative species in the study of pregnancy immunology for several reasons. First, unique aspects of the anatomy and physiology of the equine conceptus facilitate approaches that are not possible in other model organisms, such as non-surgical recovery of early stage embryos and conceptuses and isolation of pure trophoblast cell populations. Second, pregnant mares make strong cytotoxic antibody responses to paternal major histocompatibility complex class I antigens expressed by the chorionic girdle cells, permitting detailed evaluation of the antigen...
Lavoie-Lamoureux A, Moran K, Beauchamp G, Mauel S, Steinbach F, Lefebvre-Lavoie J, Martin JG, Lavoie JP.Neutrophils are potent contributors to the lung pathophysiological changes occurring in allergic airway inflammation, which typically involve T helper type 2 (Th2) cytokine overexpression. We have previously reported that equine pulmonary endothelial cells are activated by the Th2 cytokine IL-4 and express chemotactic factors for neutrophils after stimulation. We have further explored the possible mechanisms linking Th2-driven inflammation and neutrophilia by studying the effects of recombinant equine IL-4, a prototypical Th2 cytokine, on peripheral blood neutrophils (PBN) isolated from normal...
Blanchard-Channell M, Moore PF, Stott JL.Two monoclonal antibodies (mAb), UC F6G-3 and UC F13C-5, were characterized as being specific for the apparent equine homologues of CD3 and CD5, respectively. Both antibodies exhibited characteristics of pan-T-lymphocyte markers based upon immunohistology and two-colour flow cytometry. UC F6G-3 precipitated a complex of proteins (up to seven) with molecular weights ranging from 18,000 to 42,000, similar to the human and murine CD3 complex. Upon further dissociation of the precipitated complex, two proteins were identified with molecular weights of 22,000 and 27,000. Immobilized UC F6G-3 was ef...
Smith AD, Panickar KS, Urban JF, Dawson HD.Vitamins and minerals (micronutrients) play an important role in regulating and shaping an immune response. Deficiencies generally result in inadequate or dysregulated cellular activity and cytokine expression, thereby affecting the immune response. Decreased levels of natural killer, granulocyte, and phagocytic cell activity and T and B cell proliferation and trafficking are associated with inadequate levels of micronutrients, as well as increased susceptibility to various adverse health conditions, including inflammatory disorders, infection, and altered vaccine efficacy. In addition, most s...
Pacholewska A, Kraft MF, Gerber V, Jagannathan V.MicroRNAs (miRNAs) regulate post-transcriptional gene expression and may be exported from cells via exosomes or in partnership with RNA-binding proteins. MiRNAs in body fluids can act in a hormone-like manner and play important roles in disease initiation and progression. Hence, miRNAs are promising candidates as biomarkers. To identify serum miRNA biomarkers in the equine model of asthma we investigated small RNA derived from the serum of 34 control and 37 asthmatic horses. These samples were used for next generation sequencing, novel miRNA identification and differential miRNA expression ana...
