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.
Szober CM, Hauck SM, Euler KN, Fröhlich KJ, Alge-Priglinger C, Ueffing M, Deeg CA.The purpose of this study was to characterize the cell surface proteome of native compared to cultured equine retinal pigment epithelium (RPE) cells. The RPE plays an essential role in visual function and represents the outer blood-retinal barrier. We are investigating immunopathomechanisms of equine recurrent uveitis, an autoimmune inflammatory disease in horses leading to breakdown of the outer blood-retinal barrier and influx of autoreactive T-cells into affected horses' vitrei. Cell surface proteins of native and cultured RPE cells from eye-healthy horses were captured by biotinylation, an...
Go YY, Bailey E, Timoney PJ, Shuck KM, Balasuriya UB.We investigated the correlation between in vitro susceptibility of CD3(+) T lymphocytes to equine arteritis virus (EAV) infection and establishment of persistent infection among 14 stallions following natural infections. The data showed that carrier stallions with a CD3(+) T lymphocyte susceptibility phenotype to in vitro EAV infection may be at higher risk of becoming carriers than those that lack this phenotype (P = 0.0002).
Antczak DF.One of the most intriguing and dramatic examples of immunological tolerance is displayed by the mammalian foetal-placental unit, which thrives as a semi-allograft in the mother's uterus during pregnancy. The success of the so-called foetal allograft stands in stark contrast to the failure of most tissue and organ grafts to survive without genetic matching of donor and recipient or drastic immunosuppression of the recipient's immune system. Experiments conducted over the past 60 years have revealed multiple mechanisms that enable the conceptus to avoid immunological detection or destruction. Ma...
Pate DO, Clode AB, Olivry T, Cullen JM, Salmon JH, Gilger BC.To describe the immunopathologic characteristics of superficial stromal immune-mediated keratitis (IMMK) immunopathologically by characterizing cellular infiltrate in affected corneas of horses. Methods: 10 client-owned horses with IMMK. Methods: Immunohistochemical staining was performed on keratectomy samples with equine antibodies against the T-cell marker CD3 and B-cell marker CD79a (10 eyes) and the T-helper cytotoxic marker CD4 and T-cell cytotoxic marker CD8 (6 eyes). Percentage of positively stained cells was scored on a scale from 0 (no cells stained) to 4 (> 75% of cells stained)....
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...
El Garch H, Crafford JE, Amouyal P, Durand PY, Edlund Toulemonde C, Lemaitre L, Cozette V, Guthrie A, Minke JM.A recombinant canarypox virus vectored vaccine co-expressing synthetic genes encoding outer capsid proteins, VP2 and VP5, of African horse sickness virus (AHSV) serotype 4 (ALVAC(®)-AHSV4) has been demonstrated to fully protect horses against homologous challenge with virulent field virus. Guthrie et al. (2009) detected weak and variable titres of neutralizing antibody (ranging from <10 to 40) 8 weeks after vaccination leading us to hypothesize that there could be a participation of cell mediated immunity (CMI) in protection against AHSV4. The present study aimed at characterizing the CMI ind...
Hauck SM, Hofmaier F, Dietter J, Swadzba ME, Blindert M, Amann B, Behler J, Kremmer E, Ueffing M, Deeg CA.Equine recurrent uveitis is a severe and frequent blinding disease in horses which presents with auto-reactive invading T-cells, resulting in the destruction of the inner eye. Infiltration of inflammatory cells into the retina and vitreous is driven by currently unknown guidance cues, however surgical removal of the vitreous (vitrectomy) has proven therapeutically successful. Therefore, proteomic analyses of vitrectomy samples are likely to result in detection of proteins contributing to disease pathogenesis. Vitreous from healthy and ERU diseased horses were directly compared by quantitative ...
Noronha LE, Antczak DF.Pregnant mares demonstrate a reduction in cytotoxic T lymphocyte (CTL) reactivity against cells from the breeding stallion. We investigated whether this effect is limited to activity against paternal major histocompatibility complex (MHC) antigens, and whether it occurs during MHC-compatible pregnancy. Methods: Mares were mated to carry MHC-compatible or MHC-incompatible pregnancies. CTL activity of these mares when pregnant and non-pregnant was measured against cells from horses with MHC haplotypes unrelated to the mare or breeding stallion. Results: While carrying MHC-incompatible pregnancie...
Tonkin DR, Whitmore A, Johnston RE, Barro M.Replicon particles derived from Venezuelan equine encephalitis virus (VEE) are infectious non-propagating particles which act as a safe and potent systemic, mucosal, and cellular adjuvant when delivered with antigen. VEE and VEE replicon particles (VRP) can target multiple cell types including dendritic cells (DCs). The role of these cell types in VRP adjuvant activity has not been previously evaluated, and for these studies we focused on the contribution of DCs to the response to VRP. By analysis of VRP targeting in the draining lymph node, we found that VRP induced rapid recruitment of TNF-s...
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...
Wagner B, Hillegas JM, Babasyan S.CD23, also called FcεRII, is the low-affinity receptor for IgE and has first been described as a major receptor regulating IgE responses. In addition, CD23 also binds to CD21, integrins and MHC class II molecules and thus has a much wider functional role in immune regulation ranging from involvement in antigen-presentation to multiple cytokine-like functions of soluble CD23. The role of CD23 during immune responses of the horse is less well understood. Here, we expressed equine CD23 in mammalian cells using a novel IL-4 expression system. Expression resulted in high yield of recombinant IL-4/...
Pretorius A, Van Kleef M, Van Wyngaardt W, Heath J.African horsesickness (AHS) is an infectious but noncontagious viral disease affecting all species of Equidae. The recall immune response of AHSV naïve horses immunised with an attenuated African horsesickness virus serotype 4 (AHSV4) was characterised using immune assays including ELISPOT, real-time PCR (qPCR) and flow cytometry. The recall immune response detected in PBMC isolated from three inoculated horses showed an upregulation of circulating B lymphocytes that correlated with elevated IL-4 mRNA expression indicative of humoral immunity, but reduced frequency of CD4⁺ cells. In additio...
Degroote RL, Hauck SM, Kremmer E, Amann B, Ueffing M, Deeg CA.The molecular mechanism which enables activated immune cells to cross the blood-retinal barrier in spontaneous autoimmune uveitis is yet to be unraveled. Equine recurrent uveitis is the only spontaneous animal model allowing us to investigate the autoimmune mediated transformation of leukocytes in the course of this sight threatening disease. Hypothesizing that peripheral blood immune cells change their protein expression pattern in spontaneous autoimmune uveitis, we used DIGE to detect proteins with altered abundance comparing peripheral immune cells of healthy and ERU diseased horses. Among ...
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 ...
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...
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...
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...
Sun L, Adams AA, Betancourt A, Stewart JC, Liu C, Horohov DW.Interferon-gamma (IFNγ) plays an important role against viral and intracellular bacterial infections and its production is deficient in foals. Cellular proliferation provides an opportunity for de novo gene expression, though little is known about its role in regulating IFNγ expression in foals. While stimulation of foal peripheral blood mononuclear cells (PBMCs) with concanavalin A (ConA) increased the frequency of IFNγ(+) cells, the overall percentage of IFNγ(+) cells remained below that of adults. By contrast, the proliferative response of foal PBMC was significantly greater than that o...
Sears KP, Divers TJ, Neff RT, Miller WH, McDonough SP.This case report describes a 10-year-old horse that developed multiple dermal papules over the right masseter area following removal of a tick from the same site 3 months earlier. Histological examination of a biopsy from a papule was suggestive of either a T-cell-rich B-cell lymphoma or cutaneous lymphoid hyperplasia, a form of pseudolymphoma sometimes associated with a tick bite. Positive serological testing and PCR of the biopsy sample for Borrelia in conjunction with immunohistochemical testing of the skin biopsy, the clinical history and response to treatment with doxycycline strongly sup...
Go YY, Bailey E, Cook DG, Coleman SJ, Macleod JN, Chen KC, Timoney PJ, Balasuriya UB.Previously, we have shown that horses could be divided into susceptible and resistant groups based on an in vitro assay using dual-color flow cytometric analysis of CD3+ T cells infected with equine arteritis virus (EAV). Here, we demonstrate that the differences in in vitro susceptibility of equine CD3+ T lymphocytes to EAV infection have a genetic basis. To investigate the possible hereditary basis for this trait, we conducted a genome-wide association study (GWAS) to compare susceptible and resistant phenotypes. Testing of 267 DNA samples from four horse breeds that had a susceptible or a r...
Hamza E, Gerber V, Steinbach F, Marti E.Horses are particularly prone to allergic and autoimmune diseases, but little information about equine regulatory T cells (Treg) is currently available. The aim of this study therefore was to investigate the existence of CD4(+) Treg cells in horses, determine their suppressive function as well as their mechanism of action. Freshly isolated peripheral blood mononuclear cells (PBMC) from healthy horses were examined for CD4, CD25 and forkhead box P3 (FoxP3) expression. We show that equine FoxP3 is expressed constitutively by a population of CD4(+) CD25(+) T cells, mainly in the CD4(+) CD25(high)...
Regan DP, Aarnio MC, Davis WS, Carmichael KP, Vandenplas ML, Lauderdale JD, Moore PA.Equine recurrent uveitis (ERU) is a spontaneous disease that is the most common cause of blindness in horses, affecting up to 15% of the horse population. Th17 cells are a major cell population driving the pathogenesis in several mouse models of autoimmune inflammation, including experimental autoimmune uveitis. The purpose of this study is to investigate the role a Th17 cell-mediated response plays in the pathogenesis of ERU. Methods: Banked, Davidson's-fixed equine globes histopathologically diagnosed with ERU (n = 7) were compared immunohistochemically with healthy control globes (n = 7). I...
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...
Lin YZ, Shen RX, Zhu ZY, Deng XL, Cao XZ, Wang XF, Ma J, Jiang CG, Zhao LP, Lv XL, Shao YM, Zhou JH.The EIAV (equine infectious anemia virus) multi-species attenuated vaccine EIAV(DLV121) successfully prevented the spread of equine infectious anemia (EIA) in China in the 1970s and provided an excellent model for the study of protective immunity to lentiviruses. In this study, we compared immune responses induced by EIAV(DLV121) to immunity elicited by the virulent EIAV(LN40) strain and correlated immune responses to protection from infection. Horses were randomly grouped and inoculated with either EIAV(DLV121) (Vaccinees, Vac) or a sublethal dose of EIAV(LN40) (asymptomatic carriers, Car). C...
Mair TS, Pearson GR, Scase TJ.Three mature horses presented with progressive weight loss, inappetence, ventral abdominal oedema and lethargy. Two of the animals had intermittent signs of low grade abdominal pain. At presentation, all 3 had hypoalbuminaemia; 2 had hyperfibrinogenaemia and the other had neutrophilia. An oral glucose tolerance test was performed in 2 cases, both of which demonstrated impaired glucose absorption. One pony treated with corticosteroids failed to improve and developed peritonitis and was subjected to euthanasia after 2 weeks. One pony had small intestinal biopsies obtained via a standing flank la...
Pusterla N, Mapes S, Gebhart C.The cell-mediated immune response to Lawsonia intracellularis, the agent of equine proliferative enteropathy (EPE), was investigated in vaccinated and naturally infected foals. Interferon (IFN)-γ gene expression was determined in peripheral blood mononuclear cells collected from vaccinated (n=6) and control foals (n=6) every 30 days for 180 days following first vaccine administration, and from clinically affected foals (n=16) within 7-10 days of diagnosing EPE. Seroconversion (immunoperoxidase monolayer assay titer ≥60) occurred in 5/6 vaccinated foals between 60 and 90 days following the f...
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...
Moran G, Buechner-Maxwell VA, Folch H, Henriquez C, Galecio JS, Perez B, Carrasco C, Barria M.Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition similar to human asthma caused by exposure of susceptible horses to poorly ventilated stable environments. The disease is characterized by neutrophilic airway inflammation, mucus hypersecretion and reversible bronchoconstriction. This inflammatory process is mediated by several factors, including antibodies, cytokines, resident cells of the airway and inflammatory cellular components that arrive in the respiratory tract. An increasing body of evidence has lent support to the concept that a dysregulatio...
du Toit N, Genovese LM, Dalziel RG, Smith SH.A 36-year-old donkey developed dyspnoea, pyrexia, hypoalbuminaemia and oedema. Following continued clinical deterioration the donkey was humanely destroyed. Grossly, there were numerous nodules (5-10mm) scattered throughout the lung. Microscopically, the lung was infiltrated by an angiocentric and bronchocentric to diffuse mixed population of small mature and atypical lymphocytes, histiocytes, plasma cells and fewer eosinophils. The infiltrate was composed of numerous small mature and fewer atypical CD3(+) T lymphocytes. Low numbers of CD20(+) and CD79a(+) B cells, some atypical, accompanied t...
Kammerer R, Ballesteros A, Bonsor D, Warren J, Williams JM, Moore T, Dveksler G.In early equine pregnancy, a highly invasive trophoblast cell subpopulation, the chorionic girdle cells, invade the endometrium and form endometrial cups (EC). These cells express classical MHC molecules, thereby stimulating a humoral and cellular immune response, resulting in a massive accumulation of maternal CD4+ and CD8+ T cells around the EC. Nevertheless, no immediate destruction of endometrial cups by maternal lymphoid cells occurs, presumably due to immune tolerance. Although the environment of EC is rich in TGFB and in FOXP3+, CD4+ T cells, the mechanisms leading to tolerance have not...
Delcambre GH, Liu J, Streit WJ, Shaw GPJ, Vallario K, Herrington J, Wenzlow N, Barr KL, Long MT.West Nile virus (WNV), a mosquito borne member of the Flaviviridae, is one of the most commonly diagnosed agents of viral encephalitis in horses and people worldwide. Objective: A cassette of markers for formalin-fixed paraffin-embedded tissue and an archive of tissues from experimental infections in the horse were used to investigate the equine neuroimmune response to WNV meningoencephalomyelitis to phenotype the early response to WNV infection in the horse. Methods: Quantitative analysis using archived tissue from experimentally infected horses. Methods: The thalamus and hindbrain from 2 gro...
Felsburg PJ, Somberg RL, Perryman LE.This review describes the clinical, immunologic and pathologic features of two naturally-occurring models of severe combined immunodeficiency (SCID) in domestic animals that represent different forms of human SCID. Canine X-linked SCID (XSCID) has an X-linked recessive mode of inheritance and, as such, represents a model for the most common form of human SCID in the United States. Affected dogs have normal percentages of circulating B cells and low to normal percentages of phenotypically mature, but nonfunctional T cells. Severe combined immunodeficiency in the horse is an autosomal recessive ...
Paillot R, Kydd JH, MacRae S, Minke JM, Hannant D, Daly JM.Equine influenza virus (EIV) is a leading cause of respiratory disease in horses. Equine influenza infection induces a long-term immunity to re-infection. Recent strategies of vaccination aim to mimic this immunity by stimulating both antibody and cellular immune responses. Cell-mediated immunity (CMI) to influenza is well defined in man, but little has been done to characterise the responses in the horse. Additionally, the development of reliable assays for the measurement of equine CMI has lagged behind serological methods and vaccine development. In this study, two methods of measuring EIV-...
Harris SP, Hines MT, Mealey RH, Alperin DC, Hines SA.Rhodococcus equi is an important respiratory pathogen of young foals for which a vaccine has long been sought. Two major impediments to effective vaccination are the functionally immature type I immune responses of neonatal foals and early exposure to the bacterium via the environment. Despite these obstacles, it appears that under specific circumstances foals can develop a protective immune response. In this study we investigated the protective mechanisms behind oral inoculation of foals with virulent R. equi bacteria. Two foals receiving an oral inoculum demonstrated accelerated development ...
Pate DO, Clode AB, Olivry T, Cullen JM, Salmon JH, Gilger BC.To describe the immunopathologic characteristics of superficial stromal immune-mediated keratitis (IMMK) immunopathologically by characterizing cellular infiltrate in affected corneas of horses. Methods: 10 client-owned horses with IMMK. Methods: Immunohistochemical staining was performed on keratectomy samples with equine antibodies against the T-cell marker CD3 and B-cell marker CD79a (10 eyes) and the T-helper cytotoxic marker CD4 and T-cell cytotoxic marker CD8 (6 eyes). Percentage of positively stained cells was scored on a scale from 0 (no cells stained) to 4 (> 75% of cells stained)....
Lawler DF, Hopkins J, Watson ED.Recent evidence indicates that the cells of the immune system and their large network of secretory products, or cytokines, play an active role in the ovary throughout the oestrous cycle. In the present study, immune cell populations (T and B lymphocytes, macrophages, granulocytes and eosinophils) and expression of major histocompatibility complex (MHC) class II were investigated in corpora lutea from mares in early (days 2-4), mid- (days 7-10) and late (days 12-14) dioestrus, the post-luteolytic phase (days 16-17) and early pregnancy. The number of T lymphocytes within the corpus luteum increa...
Zhang W, Auyong DB, Oaks JL, McGuire TC.Two defined cytotoxic T lymphocyte (CTL) epitopes from equine infectious anemia virus (EIAV)-infected horses, equine leukocyte alloantigen (ELA)-A5.1-restricted epitope 18a, and ELA-A9-restricted epitope 28b-1 were evaluated for conservation among three wild-type EIAV strains. Epitope 18a variation occurred in all three wild-type EIAV strains, while epitope 28b-1 varied in one strain. Further, 12% amino acid changes occurred in the Gag proteins of a recently isolated wild-type strain, documenting a much greater Gag protein variation than previously reported. Evaluation of epitope 18a among two...
Wyatt CR, Davis WC, McGuire TC, Perryman LE.Six monoclonal antibodies reacting with equine T lymphocytes at different stages of maturation were selected from antibodies produced against lymphoid cell preparations. EqT12 and EqT13 antibodies identified subsets of cortical thymocytes with high terminal deoxynucleotidyltransferase (TdT) activity and no phytolectin responsiveness. EqT12+ thymocytes were scattered throughout the cortex while EqT13+ thymocytes were located in the subcapsular cortex. EqT12 bound to small numbers of bone marrow cells, splenocytes, and circulating lymphoid cells, but not to mature T lymphocytes. EqT13 bound to v...
Lonning SM, Zhang W, Leib SR, McGuire TC.Cytotoxic T lymphocytes (CTL) appear to be critical in resolving or reducing the severity of lentivirus infections. Retroviral vectors expressing the Gag/Pr or SU protein of the lentivirus equine infectious anemia virus (EIAV) were constructed and used to evaluate EIAV-specific CTL responses in horses. Three promoters, cytomegalovirus, simian virus SV40, and Moloney murine sarcoma virus (MoMSV) long terminal repeat (LTR), were used, and there was considerable variation in their ability to direct expression of Gag/Pr and SU. Vectors expressing EIAV proteins under the direction of MoMSV LTR and ...
Lunn DP, Holmes MA, Duffus WP.This paper describes the characteristics of a monoclonal antibody (CVS10) that reacts with an equine leukocyte antigen. On the basis of tissue distribution and biochemical characteristics, this antigen is equine MHC II. The equine MHC II antigen was found on a large subset of T-lymphocytes in addition to all B-lymphocytes, as has been reported previously. In addition MHC II was found to be present on a large proportion of both the mutually exclusive equine T-lymphocyte subpopulations which express either the equine homologues of CD4, or CD8. In a study of changes in equine MHC II expression wi...
McGuire TC, Zhang W, Hines MT, Henney PJ, Byrne KM.Horses with equine infectious anemia virus (EIAV) have episodes of viremia and disease; however, most eventually become inapparent carriers. A possible mechanism of control is cytotoxic T lymphocytes (CTL). To evaluate CTL in inapparent carriers with low viral loads, peripheral blood mononuclear cells (PBMC) were stimulated in vitro with autologous EIAV-infected PBMC and human IL-2 to detect memory CTL (CTLm). In initial studies, three carriers had CTLm and one of these had low-level effector CTL (CTLe). The CTLm were restricted by equine lymphocyte alloantigen-A (ELA-A) locus encoded MHC clas...
Hammond SA, Horohov D, Montelaro RC.Naive T cells can be activated both in vivo and in vitro by specialized antigen presenting cells, dendritic cells (DC), with potent antigen-specific, immunostimulatory activity. Indeed, DC can provide an extremely powerful and important immunological tool by which to potentiate the immune response for specific recognition of foreign antigens. Until recently, the direct isolation of DC from PBMC required laborious procedures with extremely poor yields (<0.1%). Methods have been developed for the human, lower primate, and murine model systems to propagate large numbers of DC from PBMC or bone...
Dohmann K, Wagner B, Horohov DW, Leibold W.In the present study, we describe the expression of equine IL2 and IL4. The cDNA of equine IL2 or IL4 was cloned in a mammalian expression vector, containing c-terminal myc- and six histidines His(6)-epitopes for recognition and purification of equine cytokines. The vector constructs were used for transfection of chinese hamster ovary (CHO) cells. Purified equine cytokines were characterised by western blotting. Equine IL2 was secreted with a molecular weight of approximately 17.1kDa, whereas IL4 was expressed in three different sizes of 17.1, 19.6 and 22.1kDa, probably due to different glycos...
Baker JM, Bamford AI, Antczak DF.Maternal immune recognition of the developing conceptus in equine pregnancy is characterized by the strongest and most consistent alloantibody response described in any species, a response directed almost exclusively against paternal MHC class I Ags. This work investigated the cellular immune response to paternal MHC Ags in pregnant and nonpregnant horses and donkeys, and in horses carrying interspecies hybrid mule conceptuses. We observed profound decreases in classical, MHC-restricted, CTL activity to allogeneic paternal cells in peripheral blood lymphocytes from both horse mares and donkey ...
Chung C, Mealey RH, McGuire TC.Cytotoxic T lymphocytes (CTL) are critical for lentivirus control including EIAV. Since CTL from most EIAV carrier horses recognize Gag epitope clusters (EC), the hypothesis that carrier horses would have high functional avidity CTL to optimal epitopes in Gag EC was tested. Twenty-two optimal EC epitopes were identified; two in EC1, six in EC2, and seven each in EC3 and 4. However, only five of nine horses had high functional avidity CTL (<or=11 nM) recognizing six epitopes in EC; four in relatively conserved EC3; and one each in EC1 and 2. Horses with high functional avidity CTL had signif...
Dixon JB, Jenkins P, Allan D.Culture of murine lymph node cells together with living protoscolices of Echinococcus granulosus is described. The presence of the parasite induced potent blastic transformation in lymphocytes of unimmunized mice as indicated by tritiated thymidine incorporation. The response was markedly reduced by killing the parasite immediately prior to culture. No blastogenic activity was detectable in supernatants from living parasites cultured alone. Protoscolices from artificially infected syngeneic mice were effective stimuli, as were protoscolices from naturally infected horse and sheep. Stimulation ...
Mählmann K, Hamza E, Marti E, Dolf G, Klukowska J, Gerber V, Koch C.Recent studies suggest that regulatory T cells (Tregs) are associated with disease severity and progression in papilloma virus induced neoplasia. Bovine papilloma virus (BPV) is recognised as the most important aetiological factor in equine sarcoid (ES) disease. The aim of this study was to compare expression levels of Treg markers and associated cytokines in tissue samples of ES-affected equids with skin samples of healthy control horses. Eleven ES-affected, and 12 healthy horses were included in the study. Expression levels of forkhead box protein 3 (FOXP3), interleukin 10 (IL10), interleuki...
Moran G, Buechner-Maxwell VA, Folch H, Henriquez C, Galecio JS, Perez B, Carrasco C, Barria M.Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition similar to human asthma caused by exposure of susceptible horses to poorly ventilated stable environments. The disease is characterized by neutrophilic airway inflammation, mucus hypersecretion and reversible bronchoconstriction. This inflammatory process is mediated by several factors, including antibodies, cytokines, resident cells of the airway and inflammatory cellular components that arrive in the respiratory tract. An increasing body of evidence has lent support to the concept that a dysregulatio...
Soboll G, Whalley JM, Koen MT, Allen GP, Fraser DG, Macklin MD, Swain WF, Lunn DP.Equine herpesvirus-1 (EHV-1) causes serious disease in horses throughout the world, despite the frequent use of vaccines. CTLs are thought to be critical for protection from primary and reactivating latent EHV-1 infections. However, the antigen-specificity of EHV-1-specific CTLs is unknown. The aim of this study was to identify EHV-1 genes that encode proteins containing CTL epitopes and to determine their MHC I (or ELA-A in the horse) restriction. Equine dendritic cells, transfected with a series of EHV-1 genes, were used to stimulate autologous CTL precursor populations derived from previous...
Porcellato I, Mecocci S, Mechelli L, Cappelli K, Brachelente C, Pepe M, Orlandi M, Gialletti R, Passeri B, Ferrari A, Modesto P, Ghelardi A....Penile squamous cell carcinomas (SCCs) are common tumors in older horses, with poor prognosis mostly due to local invasion and recurrence. These tumors are thought to be mainly caused by papillomavirus type 2 (EcPV-2). The aim of this study is to characterize the tumor immune environment (TIME) in equine penile tumors. Equine penile epithelial tumors (17 epSCCs; 2 carcinomas , CIS; 1 papilloma, P) were retrospectively selected; immune infiltrate was assessed by histology and immunohistochemistry; RT-qPCR tested the expression of selected chemokines and EcPV-2 DNA and RNA. The results confirme...
Sellon DC, Knowles DP, Greiner EC, Long MT, Hines MT, Hochstatter T, Hasel KM, Ueti M, Gillis K, Dame JB.Sarcocystis neurona is an apicomplexan parasite that is the primary etiologic agent of equine protozoal myeloencephalitis in horses. Protective immune responses in horses have not been determined, but interferon-gamma (IFN-gamma) is considered critical for protection from neurologic disease in mice. The role of adaptive and innate immune responses in control of parasites was explored by infecting BALB/c, IFN-gamma knockout (GKO), and severe combined immune deficient (SCID) mice with S. neurona (10(4) sporocysts/mouse). Immune competent BALB/c mice eliminated parasites within 30 days, with no s...
Zipplies JK, Hauck SM, Schoeffmann S, Amann B, van der Meijden CH, Stangassinger M, Ueffing M, Deeg CA.Equine recurrent uveitis (ERU) is an incurable disease affecting the inner eye that leads to blindness, through activated T cells that pass the blood-retinal barrier and destroy the retina. Serum markers are a desirable choice for monitoring development of disease, as serum is easy accessible and the markers could serve to predict the beginning of disease or an imminent relapse. Methods: In this study, serum proteomes (depleted of high-abundance serum proteins) of horses with ERU and healthy controls were compared with the 2-D DIGE (two-dimensional gel electrophoresis) technique to identify di...
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 ...
Pinto NI, McMullen RJ, Linder KE, Cullen JM, Gilger BC.To describe the clinical, histopathologic and immunohistochemical characteristics of an equine ocular inflammatory disease resulting in anterior uveitis and corneal endothelial inflammation associated with iris pigment dispersion and retrocorneal fibrous membrane (RFM) formation. Methods: Retrospective study. Methods: Sixteen horses with evidence of pigmented keratic precipitates (KPs), corneal edema, and/or iris depigmentation. Information collected from the medical records included signalment, clinical signs, prereferral treatment duration and response to therapy, ophthalmic examination find...
Charan S, Palmer K, Chester P, Mire-Sluis AR, Meager A, Edington N.Up to 21 days after exposure to live or ultraviolet-inactivated equid herpesvirus type-1 (EHV-1) autologous serum from ponies caused an immunosuppressive effect if incorporated into T-cell proliferation assays to EHV-1. The suppressive factor in the sera of ponies also inhibited T-cell response to phytohaemagglutinin. Increased levels of circulating activated transforming growth factor-beta 1 (TGF-beta 1) were detected, and the suppressive activity of the serum could be reversed by antibody to TGF-beta 1. In a challenge experiment the ponies which exhibited circulating TGF-beta 1 activity succ...
Morrison LR, Freel K, Henderson I, Hahn C, Smith SH.Lymphoma (malignant lymphoma, lymphosarcoma) is uncommon in horses in the United Kingdom. This report describes an unusual form of lymphoproliferative disease with features of lymphoma restricted to the central nervous system (CNS) and with no evidence of a primary lesion elsewhere. Immunohistochemical examination defined an overwhelming predominance of T lymphocytes with admixed B lymphocytes and activated macrophages. This case exemplifies the challenges associated with definitive diagnosis of lymphoproliferative disease of the equine CNS.
Mungun-Ochir B, Horiuchi N, Altanchimeg A, Koyama K, Suganuma K, Nyamdolgor U, Watanabe KI, Baatarjargal P, Mizushima D, Battur B, Yokoyama N....Dourine is an equine protozoan disease caused by Trypanosoma equiperdum. Dourine-afflicted animals die after developing neurological clinical signs, such as unilateral paresis. The disease has been a problem for many years; however, the pathogenesis regarding the neurological clinical signs of dourine has been unclear. In the present study, we conducted a histopathological examination in order to investigate the mechanisms by which dourine-afflicted horses develop the accompanying neurological clinical signs. Four dourine-afflicted horses in Mongolia were evaluated. An apparently healthy horse...
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...
Giessler KS, Samoilowa S, Soboll Hussey G, Kiupel M, Matiasek K, Sledge DG, Liesche F, Schlegel J, Fux R, Goehring LS.Upper respiratory tract infections with Equid Herpesvirus 1 (EHV-1) typically result in a peripheral blood mononuclear cell-associated viremia, which can lead to vasculopathy in the central nervous system. Primary EHV-1 infection also likely establishes latency in trigeminal ganglia (TG) via retrograde axonal transport and in respiratory tract-associated lymphatic tissue. However, latency establishment and reactivation are poorly understood. To characterize the pathogenesis of EHV-1 latency establishment and maintenance, two separate groups of yearling horses were experimentally infected intra...
