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.
Maloney SM, Shaw TM, Nennig KM, Larsen MS, Shah A, Kumar A, Marcotrigiano J, Grove J, Snijder EJ, Kirchdoerfer RN, Bailey AL.Arteriviruses are a family of single-stranded, positive-sense RNA (+ssRNA) viruses that infect diverse animal hosts. Many arteriviruses are macrophage-tropic, consistent with their utilization of the macrophage-specific molecule CD163 as a receptor. However, the horse arterivirus (equine arteritis virus, EAV), which infects additional cell types beyond macrophages, does not utilize CD163 in its entry mechanism. Here, we use a genome-wide CRISPR knockout screen to identify alternative receptors that could explain this discrepancy in arterivirus receptor utilization and tropism, identifying the ...
B B, G M, L G, G A, B B, T F, A G, D B, A K, G T, G S, A B, M F, L R.Equine penile tumors are common in horses and are often related to infection with equine papillomavirus type 2 (EcPV2). This study investigated the immune cell infiltrate (ICI) of these tumors in horses, focusing on the role of EcPV2. Using multiplex immunohistochemistry (mIHC) for CD3, CD20, and IBA-1 and immunohistochemistry (IHC) for FoxP3, 27 horses with papillomas (5/27), in situ carcinomas (CISs) (3/27), and squamous cell carcinomas (SCCs) (19/27) were evaluated. Eighteen cases tested positive for EcPV2 by either or both in situ hybridization (ISH) and polymerase chain reaction (PCR) (18...
Perzyna M, Grzędzicka J, Milczek-Haduch D, Dąbrowska I, Trela M, Pawliński B, Witkowska-Piłaszewicz O.Donkeys are routinely vaccinated with protocols developed for horses, yet species-specific data on their immune responses are limited. Objective: We hypothesized that donkeys exhibit robust T-cell-mediated immunity and regulatory adaptation after vaccination, comparable to horses. Methods: Thirty-six healthy, seronegative donkeys (34 mares, 2 stallions), aged 0.5-23 years (median 8 years), from two farms with similar housing and management conditions. Methods: Prospective study. Animals were selected based on clinical health assessment and confirmed seronegativity for tetanus and equine in...
da Silveira BP, Kahn SK, Legere RM, Bray JM, Cole-Pfeiffer HM, Golding MC, Cohen ND, Bordin AI.Using a horse foal model, we show that enteral immunization of newborn foals with Rhodococcus equi overcomes neonatal vaccination challenges by reprogramming innate immune responses, inducing R. equi-specific adaptive humoral and cell-mediated immune responses and protecting foals against experimental pneumonia challenge. Foals were immunized twice via gavage of R. equi (immunized group) or saline (control group) at ages 1 and 3 days. At age 28 days, all foals were challenged intrabronchially with R. equi. Post-challenge, all 5 immunized foals remained healthy, whereas 67% (4/6) of control foa...
Giercuszkiewicz-Hecold B, Pajuelo D, Steczkiewicz Z, Cywinska A, Marycz K.Astaxanthin, a strong antioxidant carotenoid, has shown promising features in mitigating inflammation and oxidative stress and so that has been considered as a supplement for high-performance animals. In this study, we aimed to evaluate the effects of astaxanthin on oxidative stress, inflammation, and mitochondrial health in peripheral blood mononuclear cells (PBMC) isolated from Arabian racehorses. Horse-derived peripheral blood mononuclear cells exposed to hydrogen peroxide (H₂O₂) presented increased reactive oxygen species (ROS) accumulation and overexpression of pro-inflammatory cytoki...
The objective of the present study was to investigate the influence of daily rhythms on the immune and inflammatory systems in horses, considering white blood cell count (WBCs), leukocyte subpopulations (neutrophils, basophils, eosinophils, lymphocytes, and monocytes), CD4+, and CD8+ lymphocyte populations, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Ten Italian Saddle horses (7-12 years old, body weight 480 ± 30 kg) underwent blood sampling every 4 h over a 24-h period. The COSINOR method was used to identify rhythms and their parameters. A one-way ...
Qiu Y, Jiang J, Yi X, Wang S, Sun X.This study investigated the immunoglobulins (IG) gene locus structure and expression diversity in local Chinese horse and donkey breeds, including Ningqiang, Guanzhong horses, and varieties such as Guanzhong, Jiami, and Northern Shaanxi donkey using genome alignment and high-throughput sequencing. The aim was to expand understanding of IG expression patterns in horses, donkeys, and their different breeds. The results revealed that the donkey IGH locus contains 117 VH genes (23 functional), 44 DH genes, and 8 JH genes, arranged in a VH-DH-JH sequence on chromosome 7, spanning approximately 1189...
Fegraeus K, Riihimäki M, Nordlund J, Akula S, Wernersson S, Raine A.Single-cell RNA sequencing (scRNA-seq) is a valuable tool for investigating cellular heterogeneity in diseases such as equine asthma (EA). This study evaluates the HIVE™ scRNA-seq method, a pico-well-based technology, for processing bronchoalveolar lavage (BAL) cells from horses with EA. The HIVE method offers practical advantages, including compatibility with both field and clinical settings, as well as a gentle workflow suited for handling sensitive cells. Our results show that the major cell types in equine BAL were successfully identified; however, the proportions of T cells and macropha...
Stafford LS, Plummer CE, Smith WC, Gibson DJ, Sharma J, Vicuna V, Diakite S, Larkin J.Recurrent uveitis (RU), an autoimmune disease, is a leading cause of ocular detriment in humans and horses. Equine and human RU share many similarities including spontaneous disease and aberrant cytokine signaling. Reduced levels of SOCS1, a critical regulator of cytokine signaling, is associated with several autoimmune diseases. Topical administration of SOCS1-KIR, a peptide mimic of SOCS1, was previously correlated to reduced ocular pathologies within ERU patients. Unassigned: To further assess the translational potential of a SOCS1 mimetic to treat RU, we assessed peptide-mediated modulatio...
Migdał A, Migdał Ł, Oczkowicz M, Tombarkiewicz B, Okólski A.Colostrum contains substances such as hormones, enzymes, polyamides, nucleic acid derivatives, and amino acid derivatives and also includes immunomodulating substances, proline-rich polypeptides, immunoglobulins (Ig) as well as bacteriostatic compounds. The aim of the study was to evaluate the impact of colostral Ig on the level of expression of selected Toll-like receptor genes (TLR3, TLR4, and TLR7). The experiments were conducted on 25 Polish Pony foals. Blood samples were collected according to the following scheme: before first suckling, at the 1st, 3rd, 5th, 10th, 20th, and 30th, day of ...
Söth R, Hoffmann ALC, Deeg CA.Equine recurrent uveitis (ERU) is a spontaneously occurring autoimmune disease and one of the leading causes of blindness in horses worldwide. Its similarities to autoimmune-mediated uveitis in humans make it a unique spontaneous animal model for this disease. Although many aspects of ERU pathogenesis have been elucidated, it remains not fully understood and requires further research. CD4+ T cells have been a particular focus of research. In a previous study, we showed metabolic alterations in CD4+ T cells from ERU cases, including an increased basal oxygen consumption rate (OCR) and elevated ...
Ammons DT, Chow L, Goodrich L, Bass L, Larson B, Williams ZJ, Stoneback JW, Dow S, Pezzanite LM.Osteoarthritis (OA) is a major source of pain and disability worldwide. Understanding of disease progression is evolving, but OA is increasingly thought to be a multifactorial disease in which the innate immune system plays a role in regulating and perpetuating low-grade inflammation. The aim of this study was to enhance our understanding of OA immunopathogenesis through characterization of the transcriptomic responses in OA joints, with the goal to facilitate the development of targeted therapies. Unassigned: Single-cell RNA sequencing (scRNA-seq) was completed on cells isolated from the syno...
In this paper, we report a comprehensive and consistent annotation of the locus encoding the β-chain of the equine T-cell receptor (TRB), as inferred from recent genome assembly using bioinformatics tools. The horse TRB locus spans approximately 1 Mb, making it the largest locus among the mammalian species studied to date, with a significantly higher number of genes related to extensive duplicative events. In the region, 136 TRBV (belonging to 29 subgroups), 2 TRBD, 13 TRBJ, and 2 TRBC genes, were identified. The general genomic organization resembles that of other mammals, with a V cluster o...
Kader T, Lin JR, Hug C, Coy S, Chen YA, de Bruijn I, Shih N, Jung E, Pelletier RJ, Leon ML, Mingo G, Omran DK, Lee JS, Yapp C, Satravada BA, Kundra R....High-Grade Serous Ovarian Cancer (HGSOC) originates from fallopian tube (FT) precursors. However, the molecular changes that occur as precancerous lesions progress to HGSOC are not well understood. To address this, we integrated high-plex imaging and spatial transcriptomics to analyze human tissue samples at different stages of HGSOC development, including p53 signatures, serous tubal intraepithelial carcinomas (STIC), and invasive HGSOC. Our findings reveal immune modulating mechanisms within precursor epithelium, characterized by chromosomal instability, persistent interferon (IFN) signaling...
Holmes CM, Wagner B.Equine herpesvirus type 1 (EHV-1) enters through the upper respiratory tract (URT). Mucosal immunity at the URT is crucial in limiting viral infection and morbidity. Here, intranasal immune cells were collected from horses (n = 15) during an experimental EHV-1 infection. CD4+ and CD8+ T cells were the major intranasal cell populations before infection and increased significantly by day six and fourteen post-infection, respectively. Nasal mucosal T cells were further characterized in healthy horses. Compared to peripheral blood mononuclear cells (PBMC), mucosal CD8+ T-cell percentages were elev...
Wjst VF, Lübke S, Wagner B, Rhyner C, Jentsch MC, Arnold C, Lohmann KL, Schnabel CL.Equine asthma (EA) is a common disease of adult horses with chronic respiratory pathology and common neutrophilic airway inflammation. It presents with hyperreactivity to hay dust components such as molds, and underlying dysregulated T cell responses have been suggested. Thus far, T cells have been analysed in EA with conflicting results and the antigen reactivity of T cells has not been demonstrated. Serological and epidemiological data point to the relevance of as an antigen source in EA. Here, we aimed to identify and characterise antigen-reactive T cells in EA. Unassigned: Cryopreserved ...
Fedorka CE, Scoggin KE, El-Sheikh Ali H, Troedsson MHT.The interleukin (IL)-6 family of cytokines is grouped by a common receptor subunit (gp130), but functions in distinct but overlapping physiological activities, including regulation of acute phase reaction and the balance between effector and regulatory T cell populations-both of which play a role in successful pregnancy maturation. Methods: Here, we aim to assess the expression profiles of members of the IL-6 cytokine family throughout equine gestation. To do so, RNA Sequencing was performed on chorioallantois and endometrium of mares at 120, 180, 300, and 330 days of gestation (n = 4/stage), ...
Cequier A, Vázquez FJ, Vitoria A, Bernad E, Fuente S, Serrano MB, Zaragoza MP, Romero A, Rodellar C, Barrachina L.The effectiveness and safety of allogeneic mesenchymal stem/stromal cells (MSCs) can be affected by patient's immune recognition. Thus, MSC immunogenicity and their immunomodulatory properties are crucial aspects for therapy. Immune responses after allogeneic MSC administration have been reported in different species, including equine. Interactions of allogenic MSCs with the recipient's immune system can be influenced by factors like matching or mismatching for the major histocompatibility complex (MHC) between donor-recipient, and by the levels of MHC expression in MSCs. The latter can vary u...
Veiga IB, Affolter VK, Moore PF, Maia-Nussbaumer PJ, Gerber V, Unger L, Dettwiler M.This report describes a multicentric intermediate-size B-cell lymphoma with epitheliotropism in a Freiberger mare affecting multiple mucous membranes, skin and internal organs. The clonal neoplastic B-cell population was accompanied by numerous reactive polyclonal small T cells. Differential diagnoses for these unusual findings are discussed. 本报告描述了一种多中心性中等大小B细胞淋巴瘤, 其在弗雷伯格母马中具有驱上皮性, 影响多处粘膜、皮肤和内脏。克隆性肿瘤B细胞群伴有大量反应性多克隆小T细胞。就这些异常发现对鉴别诊...
Wagner B.Host immune analyses require specific reagents to identify cellular and soluble components of the immune system. These immune reagents are often species-specific. For horses, various immunological tools have been developed and tested by different initiatives during the past decades. This article summarizes the development of well characterized monoclonal antibodies (mAbs) for equine immune cells, immunoglobulin isotypes, cytokines, and chemokines.
Holmes CM, Babasyan S, Wagner B.The end of gestation, ensuing parturition, and the neonatal period represent highly dynamic phases for immunological changes in both mother and offspring. The regulation of innate immune cells at the maternal-fetal interface during late term pregnancy, after birth, and during microbial colonization of the neonatal gut and other mucosal surfaces, is crucial for controlling inflammation and maintaining homeostasis. Innate immune cells and mucosal epithelial cells express antileukoproteinase (SLPI), which has anti-inflammatory and anti-protease activity that can regulate cellular activation. Unas...
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...
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 ...
Hauck SM, Dietter J, Kramer RL, Hofmaier F, Zipplies JK, Amann B, Feuchtinger A, Deeg CA, Ueffing M.Autoimmune uveitis is a blinding disease presenting with autoantibodies against eye-specific proteins as well as autoagressive T cells invading and attacking the immune-privileged target tissue retina. The molecular events enabling T cells to invade and attack the tissue have remained elusive. Changes in membrane protein expression patterns between diseased and healthy stages are especially interesting because initiating events of disease will most likely occur at membranes. Since disease progression is accompanied with a break-down of the blood-retinal barrier, serum-derived proteins mask the...
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...
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...
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...
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...
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...
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...
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...
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...
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...
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 ...
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...
Bilzer T, Planz O, Lipkin WI, Stitz L.Tissues from 9 horses and 1 donkey suffering from natural Borna disease were investigated immunomorphologically. Lymphocytic inflammatory reactions and increased expressions of MHC class I and class II antigen were found in the brain as well as in the trigeminal and olfactory system. Perivascular inflammatory infiltrates were dominated by CD4+ T cells, whereas the majority of CD8+ T cells were disseminated intraparenchymally. No evidence of inflammation was found in the retina. Borna disease virus proteins and nucleic acids were present in the hippocampus, thalamus and medulla oblongata in all...
Witkowska-Piłaszewicz O, Pingwara R, Winnicka A.Physical activity has an influence on a variety of processes in an athlete's organism including the immune system. Unfortunately, there is a lack of studies regarding racehorse immune cells, especially when the horse model is compared to human exercise physiology. The aim of the study was to determine changes in immune cell proliferation, lymphocyte populations, and monocyte functionality in trained and untrained racehorses after exercise. In this study, field data were collected. The cells from 28 racehorses (14 untrained and 14 well-trained) were collected before and after exercise (800 m at...
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...
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...
Hines SA, Stone DM, Hines MT, Alperin DC, Knowles DP, Norton LK, Hamilton MJ, Davis WC, McGuire TC.Rhodococcus equi is a gram-positive bacterium that infects alveolar macrophages and causes rhodococcal pneumonia in horses and humans. The virulence plasmid of R. equi appears to be required for both pathogenicity in the horse and the induction of protective immunity. An understanding of the mechanisms by which virulent R. equi circumvents protective host responses and by which bacteria are ultimately cleared is important for development of an effective vaccine. Six adult horses were challenged with either virulent R. equi or an avirulent, plasmid-cured derivative. By using a flow cytometric m...
Flaminio MJ, Rush BR, Davis EG, Hennessy K, Shuman W, Wilkerson MJ.Studies in infants and foals indicate an age-dependent maturation of peripheral lymphocyte subsets. The age-dependent relationship for maturation of cellular immune responses, such as phagocytosis and lymphocyte responses of the peripheral and pulmonary-derived leukocytes, has not been characterized in foals. Lymphocyte subpopulations, mitogen stimulation response of lymphocytes, lymphokine-activated killing cell activity, phagocytosis and oxidative burst activity, and serum immunoglobulin (Ig) classes G and M concentrations were determined in developing foals. This study illustrates age-depen...
Galvão AM, Ferreira-Dias G, Skarzynski DJ.In adults, physiological angiogenesis is a rare event, with few exceptions as the vasculogenesis needed for tissue growth and function in female reproductive organs. Particularly in the corpus luteum (CL), regulation of angiogenic process seems to be tightly controlled by opposite actions resultant from the balance between pro- and antiangiogenic factors. It is the extremely rapid sequence of events that determines the dramatic changes on vascular and nonvascular structures, qualifying the CL as a great model for angiogenesis studies. Using the mare CL as a model, reports on locally produced c...
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/...
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 ...
