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Home / Equine Research Bank / Immunology / Equine CD4(+) CD25(high) T cells exhibit regulatory activity...
Immunology2011; 134(3); 292-304; doi: 10.1111/j.1365-2567.2011.03489.x

Equine CD4(+) CD25(high) T cells exhibit regulatory activity by close contact and cytokine-dependent mechanisms in vitro.

Abstract: 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) subpopulation. Proliferation of CD4(+) CD25(-) sorted cells stimulated with irradiated allogenic PBMC was significantly suppressed in co-culture with CD4(+) CD25(high) sorted cells in a dose-dependent manner. The mechanism of suppression by the CD4(+) CD25(high) cell population is mediated by close contact as well as interleukin (IL)-10 and transforming growth factor-β1 (TGF-β1) and probably other factors. In addition, we studied the in vitro induction of CD4(+) Treg and their characteristics compared to those of freshly isolated CD4(+) Treg cells. Upon stimulation with a combination of concanavalin A, TGF-β1 and IL-2, CD4(+) CD25(+) T cells which express FoxP3 and have suppressive capability were induced from CD4(+) CD25(-) cells. The induced CD4(+) CD25(high) express higher levels of IL-10 and TGF-β1 mRNA compared to the freshly isolated ones. Thus, in horses as in man, the circulating CD4(+) CD25(high) subpopulation contains natural Treg cells and functional Treg can be induced in vitro upon appropriate stimulation. Our study provides the first evidence of the regulatory function of CD4(+) CD25(+) cells in horses and offers insights into ex vivo manipulation of Treg cells.
© 2011 The Authors. Immunology © 2011 Blackwell Publishing Ltd.
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Publication Date: 2011-10-08 PubMed ID: 21977999PubMed Central: PMC3209569DOI: 10.1111/j.1365-2567.2011.03489.xGoogle Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the presence and function of regulatory T cells (Treg) in horses, focusing on a specific subset, the CD4(+) CD25(high) cells, and explores their suppression mechanisms and in vitro induction.

Objective and Aim

  • The objective of this study is to explore the presence and function of regulatory T cells in horses, focusing more so on a specific variety of these cells, the CD4(+) CD25(high) cells. Given that horses are commonly susceptible to allergies and autoimmune diseases, the investigation seeks to fill a gap in the understanding of equine regulatory T cells.

Methodology

  • The researchers extracted peripheral blood mononuclear cells (PBMC) from healthy horses.
  • These obtained cells were then tested for the presence and expression of CD4, CD25 and forkhead box P3 (FoxP3) – known markers of regulatory T cells.
  • In addition, the scientists conducted tests to determine the suppressive function of these cells in interaction with other immune cells.

Findings

  • It was found that a subpopulation of CD4(+) CD25(+) T cells regularly express equine FoxP3, with higher concentrations in the CD4(+) CD25(high) subset.
  • There was significant suppression of proliferation of CD4(+) CD25(-) sorted cells when co-cultured with CD4(+) CD25(high) cells. This suppression appeared to be dose-dependent.
  • The mechanisms of suppression by CD4(+) CD25(high) cells were determined to be a combination of close contact with other cells and the action of certain chemicals known as cytokines, namely interleukin (IL)-10 and transforming growth factor-β1 (TGF-β1), amongst possible other factors.

In vitro Induction of Treg Cells

  • Moreover, the study investigated the in vitro induction of CD4(+) Treg cells and compared their characteristics with those freshly isolated.
  • When stimulated with specific agents, certain cells developed into CD4(+) CD25(+) T cells that expressed FoxP3 and exhibited suppressive properties. These ‘induced’ cells expressed higher levels of IL-10 and TGF-β1 compared to those that were freshly isolated.

Conclusion

  • The study concludes that the CD4(+) CD25(high) subpopulation of peripheral blood cells in horses contain natural regulatory T cells, and that functional Treg cells can be induced in vitro given the right stimulation.
  • This research provides the first evidence of the regulatory function of CD4(+) CD25(+) cells in horses, and thereby offers valuable insights into the manipulation of Treg cells outside the body, which could have therapeutic implications.

Cite This Article

APA
Hamza E, Gerber V, Steinbach F, Marti E. (2011). Equine CD4(+) CD25(high) T cells exhibit regulatory activity by close contact and cytokine-dependent mechanisms in vitro. Immunology, 134(3), 292-304. https://doi.org/10.1111/j.1365-2567.2011.03489.x

Publication

Immunology
ISSN: 1365-2567
NlmUniqueID: 0374672
Country: England
Language: English
Volume: 134
Issue: 3
Pages: 292-304

Researcher Affiliations

Hamza, Eman
  • Department of Clinical Research and Veterinary Public Health, University of Bern, Bern, Switzerland. eman.hamza@vetsuisse.unibe.ch
Gerber, Vinzenz
    Steinbach, Falko
      Marti, Eliane

        MeSH Terms

        • Animals
        • CD4-Positive T-Lymphocytes / cytology
        • CD4-Positive T-Lymphocytes / immunology
        • CD4-Positive T-Lymphocytes / metabolism
        • Cell Proliferation / drug effects
        • Cells, Cultured
        • Coculture Techniques
        • Cytokines / genetics
        • Cytokines / immunology
        • Cytokines / pharmacology
        • Dose-Response Relationship, Drug
        • Female
        • Flow Cytometry
        • Forkhead Transcription Factors / immunology
        • Forkhead Transcription Factors / metabolism
        • Horses / immunology
        • Horses / metabolism
        • Interleukin-10 / genetics
        • Interleukin-10 / immunology
        • Interleukin-10 / pharmacology
        • Interleukin-2 Receptor alpha Subunit / immunology
        • Interleukin-2 Receptor alpha Subunit / metabolism
        • Leukocytes, Mononuclear / cytology
        • Leukocytes, Mononuclear / immunology
        • Leukocytes, Mononuclear / metabolism
        • Male
        • Reverse Transcriptase Polymerase Chain Reaction
        • T-Lymphocytes, Regulatory / cytology
        • T-Lymphocytes, Regulatory / immunology
        • T-Lymphocytes, Regulatory / metabolism
        • Transforming Growth Factor beta1 / genetics
        • Transforming Growth Factor beta1 / immunology
        • Transforming Growth Factor beta1 / pharmacology

        References

        This article includes 89 references
        1. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.. J Immunol 1995 Aug 1;155(3):1151-64.
          pubmed: 7636184
        2. Akbar AN, Taams LS, Salmon M, Vukmanovic-Stejic M. The peripheral generation of CD4+ CD25+ regulatory T cells.. Immunology 2003 Jul;109(3):319-25.
          pmc: PMC1782989pubmed: 12807474doi: 10.1046/j.1365-2567.2003.01678.xgoogle scholar: lookup
        3. Akdis M. Immune tolerance in allergy.. Curr Opin Immunol 2009 Dec;21(6):700-7.
          pubmed: 19700272doi: 10.1016/j.coi.2009.07.012google scholar: lookup
        4. Cavani A. Immune regulatory mechanisms in allergic contact dermatitis and contact sensitization.. Chem Immunol Allergy 2008;94:93-100.
          pubmed: 18802340doi: 10.1159/000154934google scholar: lookup
        5. McGee HS, Agrawal DK. Naturally occurring and inducible T-regulatory cells modulating immune response in allergic asthma.. Am J Respir Crit Care Med 2009 Aug 1;180(3):211-25.
          pmc: PMC2724714pubmed: 19447898doi: 10.1164/rccm.200809-1505OCgoogle scholar: lookup
        6. Li Z, Arijs I, De Hertogh G, Vermeire S, Noman M, Bullens D, Coorevits L, Sagaert X, Schuit F, Rutgeerts P, Ceuppens JL, Van Assche G. Reciprocal changes of Foxp3 expression in blood and intestinal mucosa in IBD patients responding to infliximab.. Inflamm Bowel Dis 2010 Aug;16(8):1299-310.
          pubmed: 20196149doi: 10.1002/ibd.21229google scholar: lookup
        7. Marin ND, París SC, Vélez VM, Rojas CA, Rojas M, García LF. Regulatory T cell frequency and modulation of IFN-gamma and IL-17 in active and latent tuberculosis.. Tuberculosis (Edinb) 2010 Jul;90(4):252-61.
          pubmed: 20594914doi: 10.1016/j.tube.2010.05.003google scholar: lookup
        8. Ogino H, Nakamura K, Ihara E, Akiho H, Takayanagi R. CD4+CD25+ regulatory T cells suppress Th17-responses in an experimental colitis model.. Dig Dis Sci 2011 Feb;56(2):376-86.
          pubmed: 20521112doi: 10.1007/s10620-010-1286-2google scholar: lookup
        9. Boros P, Bromberg JS. Human FOXP3+ regulatory T cells in transplantation.. Am J Transplant 2009 Aug;9(8):1719-24.
          pmc: PMC2724649pubmed: 19538489doi: 10.1111/j.1600-6143.2009.02704.xgoogle scholar: lookup
        10. Racusen LC. T-regulatory cells in human transplantation.. Am J Transplant 2008 Jul;8(7):1359-60.
          pubmed: 18557721doi: 10.1111/j.1600-6143.2008.02306.xgoogle scholar: lookup
        11. Semiletova NV, Shen XD, Baibakov B, Andakyan A. Intensity of transplant chronic rejection correlates with level of graft-infiltrating regulatory cells.. J Heart Lung Transplant 2010 Mar;29(3):335-41.
          pubmed: 20080050doi: 10.1016/j.healun.2009.08.003google scholar: lookup
        12. Blatner NR, Bonertz A, Beckhove P, Cheon EC, Krantz SB, Strouch M, Weitz J, Koch M, Halverson AL, Bentrem DJ, Khazaie K. In colorectal cancer mast cells contribute to systemic regulatory T-cell dysfunction.. Proc Natl Acad Sci U S A 2010 Apr 6;107(14):6430-5.
          pmc: PMC2851977pubmed: 20308560doi: 10.1073/pnas.0913683107google scholar: lookup
        13. Erdman SE, Poutahidis T. Cancer inflammation and regulatory T cells.. Int J Cancer 2010 Aug 15;127(4):768-79.
          pmc: PMC4068033pubmed: 20518013doi: 10.1002/ijc.25430google scholar: lookup
        14. Wilczynski JR, Kalinka J, Radwan M. The role of T-regulatory cells in pregnancy and cancer.. Front Biosci 2008 Jan 1;13:2275-89.
          pubmed: 17981709doi: 10.2741/2841google scholar: lookup
        15. Steinbach F, Deeg C, Mauel S, Wagner B. Equine immunology: offspring of the serum horse.. Trends Immunol 2002 May;23(5):223-5.
          pubmed: 12102731doi: 10.1016/s1471-4906(02)02193-2google scholar: lookup
        16. Piccirillo CA, Shevach EM. Naturally-occurring CD4+CD25+ immunoregulatory T cells: central players in the arena of peripheral tolerance.. Semin Immunol 2004 Apr;16(2):81-8.
          pubmed: 15036231doi: 10.1016/j.smim.2003.12.003google scholar: lookup
        17. Raimondi G, Turner MS, Thomson AW, Morel PA. Naturally occurring regulatory T cells: recent insights in health and disease.. Crit Rev Immunol 2007;27(1):61-95.
          pubmed: 17430097doi: 10.1615/critrevimmunol.v27.i1.50google scholar: lookup
        18. Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G. Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood.. J Exp Med 2001 Jun 4;193(11):1303-10.
          pmc: PMC2193384pubmed: 11390437doi: 10.1084/jem.193.11.1303google scholar: lookup
        19. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3.. Science 2003 Feb 14;299(5609):1057-61.
          pubmed: 12522256doi: 10.1126/science.1079490google scholar: lookup
        20. Zheng Y, Rudensky AY. Foxp3 in control of the regulatory T cell lineage.. Nat Immunol 2007 May;8(5):457-62.
          pubmed: 17440451doi: 10.1038/ni1455google scholar: lookup
        21. Ziegler SF. FOXP3: of mice and men.. Annu Rev Immunol 2006;24:209-26.
          pubmed: 16551248doi: 10.1146/annurev.immunol.24.021605.090547google scholar: lookup
        22. Akdis M. T-cell tolerance to inhaled allergens: mechanisms and therapeutic approaches.. Expert Opin Biol Ther 2008 Jun;8(6):769-77.
          pubmed: 18476788doi: 10.1517/14712598.8.6.769google scholar: lookup
        23. Mittag D, Scholzen A, Varese N, Baxter L, Paukovics G, Harrison LC, Rolland JM, O'Hehir RE. The effector T cell response to ryegrass pollen is counterregulated by simultaneous induction of regulatory T cells.. J Immunol 2010 May 1;184(9):4708-16.
          pubmed: 20308632doi: 10.4049/jimmunol.0901036google scholar: lookup
        24. Commodaro AG, Peron JP, Genre J, Arslanian C, Sanches L, Muccioli C, Rizzo LV, Belfort R Jr. IL-10 and TGF-beta immunoregulatory cytokines rather than natural regulatory T cells are associated with the resolution phase of Vogt-Koyanagi-Harada (VKH) syndrome.. Scand J Immunol 2010 Jul;72(1):31-7.
          pubmed: 20591073doi: 10.1111/j.1365-3083.2010.02401.xgoogle scholar: lookup
        25. Levings MK, Sangregorio R, Sartirana C, Moschin AL, Battaglia M, Orban PC, Roncarolo MG. Human CD25+CD4+ T suppressor cell clones produce transforming growth factor beta, but not interleukin 10, and are distinct from type 1 T regulatory cells.. J Exp Med 2002 Nov 18;196(10):1335-46.
          pmc: PMC2193983pubmed: 12438424doi: 10.1084/jem.20021139google scholar: lookup
        26. Vieira PL, Christensen JR, Minaee S, O'Neill EJ, Barrat FJ, Boonstra A, Barthlott T, Stockinger B, Wraith DC, O'Garra A. IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells.. J Immunol 2004 May 15;172(10):5986-93.
          pubmed: 15128781doi: 10.4049/jimmunol.172.10.5986google scholar: lookup
        27. Biller BJ, Elmslie RE, Burnett RC, Avery AC, Dow SW. Use of FoxP3 expression to identify regulatory T cells in healthy dogs and dogs with cancer.. Vet Immunol Immunopathol 2007 Mar 15;116(1-2):69-78.
          pubmed: 17224188doi: 10.1016/j.vetimm.2006.12.002google scholar: lookup
        28. Chen W, Konkel JE. TGF-beta and 'adaptive' Foxp3(+) regulatory T cells.. J Mol Cell Biol 2010 Feb;2(1):30-6.
          pmc: PMC2905060pubmed: 19648226doi: 10.1093/jmcb/mjp004google scholar: lookup
        29. Davidson TS, DiPaolo RJ, Andersson J, Shevach EM. Cutting Edge: IL-2 is essential for TGF-beta-mediated induction of Foxp3+ T regulatory cells.. J Immunol 2007 Apr 1;178(7):4022-6.
          pubmed: 17371955doi: 10.4049/jimmunol.178.7.4022google scholar: lookup
        30. Jonuleit H, Schmitt E, Kakirman H, Stassen M, Knop J, Enk AH. Infectious tolerance: human CD25(+) regulatory T cells convey suppressor activity to conventional CD4(+) T helper cells.. J Exp Med 2002 Jul 15;196(2):255-60.
          pmc: PMC2193929pubmed: 12119350doi: 10.1084/jem.20020394google scholar: lookup
        31. Dieckmann D, Bruett CH, Ploettner H, Lutz MB, Schuler G. Human CD4(+)CD25(+) regulatory, contact-dependent T cells induce interleukin 10-producing, contact-independent type 1-like regulatory T cells [corrected].. J Exp Med 2002 Jul 15;196(2):247-53.
          pmc: PMC2193931pubmed: 12119349doi: 10.1084/jem.20020642google scholar: lookup
        32. Shevach EM. Mechanisms of foxp3+ T regulatory cell-mediated suppression.. Immunity 2009 May;30(5):636-45.
          pubmed: 19464986doi: 10.1016/j.immuni.2009.04.010google scholar: lookup
        33. Field EH, Kulhankova K, Nasr ME. Natural Tregs, CD4+CD25+ inhibitory hybridomas, and their cell contact dependent suppression.. Immunol Res 2007;39(1-3):62-78.
          pubmed: 17917056doi: 10.1007/s12026-007-0064-5google scholar: lookup
        34. Shevach EM, McHugh RS, Piccirillo CA, Thornton AM. Control of T-cell activation by CD4+ CD25+ suppressor T cells.. Immunol Rev 2001 Aug;182:58-67.
          pubmed: 11722623doi: 10.1034/j.1600-065x.2001.1820104.xgoogle scholar: lookup
        35. Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K, Akdis CA. IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy.. Eur J Immunol 2003 May;33(5):1205-14.
          pubmed: 12731045doi: 10.1002/eji.200322919google scholar: lookup
        36. Miyara M, Sakaguchi S. Natural regulatory T cells: mechanisms of suppression.. Trends Mol Med 2007 Mar;13(3):108-16.
          pubmed: 17257897doi: 10.1016/j.molmed.2007.01.003google scholar: lookup
        37. Taylor A, Verhagen J, Blaser K, Akdis M, Akdis CA. Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells.. Immunology 2006 Apr;117(4):433-42.
          pmc: PMC1782242pubmed: 16556256doi: 10.1111/j.1365-2567.2006.02321.xgoogle scholar: lookup
        38. Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo MJ. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells.. Nat Immunol 2007 Dec;8(12):1353-62.
          pubmed: 17982458doi: 10.1038/ni1536google scholar: lookup
        39. Thornton AM, Shevach EM. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production.. J Exp Med 1998 Jul 20;188(2):287-96.
          pmc: PMC2212461pubmed: 9670041doi: 10.1084/jem.188.2.287google scholar: lookup
        40. Tran DQ, Glass DD, Uzel G, Darnell DA, Spalding C, Holland SM, Shevach EM. Analysis of adhesion molecules, target cells, and role of IL-2 in human FOXP3+ regulatory T cell suppressor function.. J Immunol 2009 Mar 1;182(5):2929-38.
          pmc: PMC2777511pubmed: 19234188doi: 10.4049/jimmunol.0803827google scholar: lookup
        41. Steinbach F, Bischoff S, Freund H, Metzner-Flemisch S, Ibrahim S, Walter J, Wilke I, Mauel S. Clinical application of dendritic cells and interleukin-2 and tools to study activated T cells in horses--first results and implications for quality control.. Vet Immunol Immunopathol 2009 Mar 15;128(1-3):16-23.
          pubmed: 19056130doi: 10.1016/j.vetimm.2008.10.317google scholar: lookup
        42. Käser T, Gerner W, Hammer SE, Patzl M, Saalmüller A. Detection of Foxp3 protein expression in porcine T lymphocytes.. Vet Immunol Immunopathol 2008 Sep 15;125(1-2):92-101.
          pubmed: 18565594doi: 10.1016/j.vetimm.2008.05.007google scholar: lookup
        43. Hamza E, Doherr MG, Bertoni G, Jungi TW, Marti E. Modulation of allergy incidence in icelandic horses is associated with a change in IL-4-producing T cells.. Int Arch Allergy Immunol 2007;144(4):325-37.
          pubmed: 17671392doi: 10.1159/000106459google scholar: lookup
        44. Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA. CD4+CD25+ regulatory cells from human peripheral blood express very high levels of CD25 ex vivo.. Novartis Found Symp 2003;252:67-88; discussion 88-91, 106-14.
          pubmed: 14609213doi: 10.1002/0470871628.ch6google scholar: lookup
        45. Käser T, Gerner W, Hammer SE, Patzl M, Saalmüller A. Phenotypic and functional characterisation of porcine CD4(+)CD25(high) regulatory T cells.. Vet Immunol Immunopathol 2008 Mar 15;122(1-2):153-8.
          pubmed: 17868905doi: 10.1016/j.vetimm.2007.08.002google scholar: lookup
        46. Roncador G, Brown PJ, Maestre L, Hue S, Martínez-Torrecuadrada JL, Ling KL, Pratap S, Toms C, Fox BC, Cerundolo V, Powrie F, Banham AH. Analysis of FOXP3 protein expression in human CD4+CD25+ regulatory T cells at the single-cell level.. Eur J Immunol 2005 Jun;35(6):1681-91.
          pubmed: 15902688doi: 10.1002/eji.200526189google scholar: lookup
        47. Desjardins I, Theoret C, Joubert P, Wagner B, Lavoie JP. Comparison of TGF-beta 1 concentrations in bronchoalveolar fluid of horses affected with heaves and of normal controls.. Vet Immunol Immunopathol 2004 Oct;101(3-4):133-41.
          pubmed: 15350743doi: 10.1016/j.vetimm.2004.03.008google scholar: lookup
        48. Heimann M, Janda J, Sigurdardottir OG, Svansson V, Klukowska J, von Tscharner C, Doherr M, Broström H, Andersson LS, Einarsson S, Marti E, Torsteinsdottir S. Skin-infiltrating T cells and cytokine expression in Icelandic horses affected with insect bite hypersensitivity: a possible role for regulatory T cells.. Vet Immunol Immunopathol 2011 Mar 15;140(1-2):63-74.
          pubmed: 21168921doi: 10.1016/j.vetimm.2010.11.016google scholar: lookup
        49. Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T. Regulatory T cells: how do they suppress immune responses?. Int Immunol 2009 Oct;21(10):1105-11.
          pubmed: 19737784doi: 10.1093/intimm/dxp095google scholar: lookup
        50. Hamza E, Wagner B, Jungi TW, Mirkovitch J, Marti E. Reduced incidence of insect-bite hypersensitivity in Icelandic horses is associated with a down-regulation of interleukin-4 by interleukin-10 and transforming growth factor-beta1.. Vet Immunol Immunopathol 2008 Mar 15;122(1-2):65-75.
          pubmed: 18082270doi: 10.1016/j.vetimm.2007.10.018google scholar: lookup
        51. de la Rosa M, Rutz S, Dorninger H, Scheffold A. Interleukin-2 is essential for CD4+CD25+ regulatory T cell function.. Eur J Immunol 2004 Sep;34(9):2480-8.
          pubmed: 15307180doi: 10.1002/eji.200425274google scholar: lookup
        52. Horwitz DA, Zheng SG, Gray JD. The role of the combination of IL-2 and TGF-beta or IL-10 in the generation and function of CD4+ CD25+ and CD8+ regulatory T cell subsets.. J Leukoc Biol 2003 Oct;74(4):471-8.
          pmc: PMC7166542pubmed: 14519757doi: 10.1189/jlb.0503228google scholar: lookup
        53. Tran DQ, Ramsey H, Shevach EM. Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-beta dependent but does not confer a regulatory phenotype.. Blood 2007 Oct 15;110(8):2983-90.
          pmc: PMC2018674pubmed: 17644734doi: 10.1182/blood-2007-06-094656google scholar: lookup
        54. Wu K, Bi Y, Sun K, Wang C. IL-10-producing type 1 regulatory T cells and allergy.. Cell Mol Immunol 2007 Aug;4(4):269-75.
          pubmed: 17764617
        55. Dacre KJ, McGorum BC, Marlin DJ, Bartner LR, Brown JK, Shaw DJ, Robinson NE, Deaton C, Pemberton AD. Organic dust exposure increases mast cell tryptase in bronchoalveolar lavage fluid and airway epithelium of heaves horses.. Clin Exp Allergy 2007 Dec;37(12):1809-18.
          pubmed: 17956586doi: 10.1111/j.1365-2222.2007.02857.xgoogle scholar: lookup
        56. Deeg CA, Hauck SM, Amann B, Pompetzki D, Altmann F, Raith A, Schmalzl T, Stangassinger M, Ueffing M. Equine recurrent uveitis--a spontaneous horse model of uveitis.. Ophthalmic Res 2008;40(3-4):151-3.
          pubmed: 18421230doi: 10.1159/000119867google scholar: lookup
        57. Akbari O, Stock P, DeKruyff RH, Umetsu DT. Role of regulatory T cells in allergy and asthma.. Curr Opin Immunol 2003 Dec;15(6):627-33.
          pubmed: 14630195doi: 10.1016/j.coi.2003.09.012google scholar: lookup
        58. Bettini M, Vignali DA. Regulatory T cells and inhibitory cytokines in autoimmunity.. Curr Opin Immunol 2009 Dec;21(6):612-8.
          pmc: PMC2787714pubmed: 19854631doi: 10.1016/j.coi.2009.09.011google scholar: lookup
        59. Cavani A. T regulatory cells in contact hypersensitivity.. Curr Opin Allergy Clin Immunol 2008 Aug;8(4):294-8.
          pubmed: 18596584doi: 10.1097/ACI.0b013e3283079ea4google scholar: lookup
        60. Di Ianni M, Del Papa B, Cecchini D, Bonifacio E, Moretti L, Zei T, Ostini RI, Falzetti F, Fontana L, Tagliapietra G, Maldini C, Martelli MF, Tabilio A. Immunomagnetic isolation of CD4+CD25+FoxP3+ natural T regulatory lymphocytes for clinical applications.. Clin Exp Immunol 2009 May;156(2):246-53.
          pmc: PMC2759472pubmed: 19292855doi: 10.1111/j.1365-2249.2009.03901.xgoogle scholar: lookup
        61. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.. Nat Immunol 2003 Apr;4(4):330-6.
          pubmed: 12612578doi: 10.1038/ni904google scholar: lookup
        62. Komatsu N, Mariotti-Ferrandiz ME, Wang Y, Malissen B, Waldmann H, Hori S. Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity.. Proc Natl Acad Sci U S A 2009 Feb 10;106(6):1903-8.
          pmc: PMC2644136pubmed: 19174509doi: 10.1073/pnas.0811556106google scholar: lookup
        63. Sakaguchi S, Ono M, Setoguchi R, Yagi H, Hori S, Fehervari Z, Shimizu J, Takahashi T, Nomura T. Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease.. Immunol Rev 2006 Aug;212:8-27.
          pubmed: 16903903doi: 10.1111/j.0105-2896.2006.00427.xgoogle scholar: lookup
        64. Thongpan M, Kitiyakara C, Louischaroen Y, Keesukphan P, Chaiyaroj SC. Analysis of Foxp3, CD25, and CD127 expressed on regulatory T cells in Thai subjects.. Asian Pac J Allergy Immunol 2009 Jun-Sep;27(2-3):137-45.
          pubmed: 19839500
        65. Zelenay S, Lopes-Carvalho T, Caramalho I, Moraes-Fontes MF, Rebelo M, Demengeot J. Foxp3+ CD25- CD4 T cells constitute a reservoir of committed regulatory cells that regain CD25 expression upon homeostatic expansion.. Proc Natl Acad Sci U S A 2005 Mar 15;102(11):4091-6.
          pmc: PMC554795pubmed: 15753306doi: 10.1073/pnas.0408679102google scholar: lookup
        66. Ziegler SF, Buckner JH. Influence of FOXP3 on CD4+CD25+ regulatory T cells.. Expert Rev Clin Immunol 2006 Jul;2(4):639-47.
          pubmed: 20477619doi: 10.1586/1744666X.2.4.639google scholar: lookup
        67. Cabarrocas J, Cassan C, Magnusson F, Piaggio E, Mars L, Derbinski J, Kyewski B, Gross DA, Salomon BL, Khazaie K, Saoudi A, Liblau RS. Foxp3+ CD25+ regulatory T cells specific for a neo-self-antigen develop at the double-positive thymic stage.. Proc Natl Acad Sci U S A 2006 May 30;103(22):8453-8.
          pmc: PMC1482513pubmed: 16709665doi: 10.1073/pnas.0603086103google scholar: lookup
        68. Cambos M, Bélanger B, Jacques A, Roulet A, Scorza T. Natural regulatory (CD4+CD25+FOXP+) T cells control the production of pro-inflammatory cytokines during Plasmodium chabaudi adami infection and do not contribute to immune evasion.. Int J Parasitol 2008 Feb;38(2):229-38.
          pubmed: 17868677doi: 10.1016/j.ijpara.2007.07.006google scholar: lookup
        69. Fantini MC, Dominitzki S, Rizzo A, Neurath MF, Becker C. In vitro generation of CD4+ CD25+ regulatory cells from murine naive T cells.. Nat Protoc 2007;2(7):1789-94.
          pubmed: 17641646doi: 10.1038/nprot.2007.258google scholar: lookup
        70. Pinheiro D, Singh Y, Grant CR, Appleton RC, Sacchini F, Walker KR, Chadbourne AH, Palmer CA, Armitage-Chan E, Thompson I, Williamson L, Cunningham F, Garden OA. Phenotypic and functional characterization of a CD4(+) CD25(high) FOXP3(high) regulatory T-cell population in the dog.. Immunology 2011 Jan;132(1):111-22.
          pmc: PMC3015081pubmed: 20880379doi: 10.1111/j.1365-2567.2010.03346.xgoogle scholar: lookup
        71. Garden OA, Pinheiro D, Cunningham F. All creatures great and small: regulatory T cells in mice, humans, dogs and other domestic animal species.. Int Immunopharmacol 2011 May;11(5):576-88.
          pubmed: 21093606doi: 10.1016/j.intimp.2010.11.003google scholar: lookup
        72. Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system.. Nat Rev Immunol 2010 Jul;10(7):490-500.
          pubmed: 20559327doi: 10.1038/nri2785google scholar: lookup
        73. Gerner W, Stadler M, Hammer SE, Klein D, Saalmüller A. Sensitive detection of Foxp3 expression in bovine lymphocytes by flow cytometry.. Vet Immunol Immunopathol 2010 Nov 15;138(1-2):154-8.
          pubmed: 20701981doi: 10.1016/j.vetimm.2010.07.009google scholar: lookup
        74. Kuwana M. Induction of anergic and regulatory T cells by plasmacytoid dendritic cells and other dendritic cell subsets.. Hum Immunol 2002 Dec;63(12):1156-63.
          pubmed: 12480259doi: 10.1016/s0198-8859(02)00754-1google scholar: lookup
        75. O꯭ A, Hubert FX, Chabannes D, Gautreau L, Heslan M, Josien R. Differential control of T regulatory cell proliferation and suppressive activity by mature plasmacytoid versus conventional spleen dendritic cells.. J Immunol 2008 May 1;180(9):5862-70.
          pubmed: 18424705doi: 10.4049/jimmunol.180.9.5862google scholar: lookup
        76. Kubo T, Hatton RD, Oliver J, Liu X, Elson CO, Weaver CT. Regulatory T cell suppression and anergy are differentially regulated by proinflammatory cytokines produced by TLR-activated dendritic cells.. J Immunol 2004 Dec 15;173(12):7249-58.
          pubmed: 15585847doi: 10.4049/jimmunol.173.12.7249google scholar: lookup
        77. Scheffold A, Murphy KM, Höfer T. Competition for cytokines: T(reg) cells take all.. Nat Immunol 2007 Dec;8(12):1285-7.
          pubmed: 18026078doi: 10.1038/ni1207-1285google scholar: lookup
        78. Csencsits K, Wood SC, Lu G, Bishop DK. Transforming growth factor-beta1 gene transfer is associated with the development of regulatory cells.. Am J Transplant 2005 Oct;5(10):2378-84.
          pubmed: 16162185doi: 10.1111/j.1600-6143.2005.01042.xgoogle scholar: lookup
        79. Fantini MC, Becker C, Monteleone G, Pallone F, Galle PR, Neurath MF. Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25- T cells through Foxp3 induction and down-regulation of Smad7.. J Immunol 2004 May 1;172(9):5149-53.
          pubmed: 15100250doi: 10.4049/jimmunol.172.9.5149google scholar: lookup
        80. Yamagiwa S, Gray JD, Hashimoto S, Horwitz DA. A role for TGF-beta in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood.. J Immunol 2001 Jun 15;166(12):7282-9.
          pubmed: 11390478doi: 10.4049/jimmunol.166.12.7282google scholar: lookup
        81. Shanmugasundaram R, Selvaraj RK. In vitro human TGF-beta treatment converts CD4(+)CD25(-) T cells into induced T regulatory like cells.. Vet Immunol Immunopathol 2010 Sep 15;137(1-2):161-5.
          pubmed: 20684851doi: 10.1016/j.vetimm.2010.04.017google scholar: lookup
        82. Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3.. J Exp Med 2003 Dec 15;198(12):1875-86.
          pmc: PMC2194145pubmed: 14676299doi: 10.1084/jem.20030152google scholar: lookup
        83. Ganusov VV, Milutinović D, De Boer RJ. IL-2 regulates expansion of CD4+ T cell populations by affecting cell death: insights from modeling CFSE data.. J Immunol 2007 Jul 15;179(2):950-7.
          pubmed: 17617586doi: 10.4049/jimmunol.179.2.950google scholar: lookup
        84. Malek TR. The main function of IL-2 is to promote the development of T regulatory cells.. J Leukoc Biol 2003 Dec;74(6):961-5.
          pubmed: 12960253doi: 10.1189/jlb.0603272google scholar: lookup
        85. Gavin MA, Torgerson TR, Houston E, DeRoos P, Ho WY, Stray-Pedersen A, Ocheltree EL, Greenberg PD, Ochs HD, Rudensky AY. Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development.. Proc Natl Acad Sci U S A 2006 Apr 25;103(17):6659-64.
          pmc: PMC1458937pubmed: 16617117doi: 10.1073/pnas.0509484103google scholar: lookup
        86. Mantel PY, Ouaked N, Rückert B, Karagiannidis C, Welz R, Blaser K, Schmidt-Weber CB. Molecular mechanisms underlying FOXP3 induction in human T cells.. J Immunol 2006 Mar 15;176(6):3593-602.
          pubmed: 16517728doi: 10.4049/jimmunol.176.6.3593google scholar: lookup
        87. Walker MR, Carson BD, Nepom GT, Ziegler SF, Buckner JH. De novo generation of antigen-specific CD4+CD25+ regulatory T cells from human CD4+CD25- cells.. Proc Natl Acad Sci U S A 2005 Mar 15;102(11):4103-8.
          pmc: PMC554797pubmed: 15753318doi: 10.1073/pnas.0407691102google scholar: lookup
        88. Pillai V, Ortega SB, Wang CK, Karandikar NJ. Transient regulatory T-cells: a state attained by all activated human T-cells.. Clin Immunol 2007 Apr;123(1):18-29.
          pmc: PMC1868523pubmed: 17185041doi: 10.1016/j.clim.2006.10.014google scholar: lookup
        89. Wang J, Ioan-Facsinay A, van der Voort EI, Huizinga TW, Toes RE. Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells.. Eur J Immunol 2007 Jan;37(1):129-38.
          pubmed: 17154262doi: 10.1002/eji.200636435google scholar: lookup

        Citations

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        1. Jaworska J, de Mestre AM, Wiśniewska J, Wagner B, Nowicki A, Kowalczyk-Zięba I, Wocławek-Potocka I. Populations of NK Cells and Regulatory T Cells in the Endometrium of Cycling Mares-A Preliminary Study.. Animals (Basel) 2022 Nov 30;12(23).
          doi: 10.3390/ani12233373pubmed: 36496894google scholar: lookup
        2. Cequier A, Romero A, Vázquez FJ, Vitoria A, Bernad E, Fuente S, Zaragoza P, Rodellar C, Barrachina L. Equine Mesenchymal Stem Cells Influence the Proliferative Response of Lymphocytes: Effect of Inflammation, Differentiation and MHC-Compatibility.. Animals (Basel) 2022 Apr 11;12(8).
          doi: 10.3390/ani12080984pubmed: 35454231google scholar: lookup
        3. Kamm JL, Riley CB, Parlane NA, Gee EK, McIlwraith CW. Immune response to allogeneic equine mesenchymal stromal cells.. Stem Cell Res Ther 2021 Nov 12;12(1):570.
          doi: 10.1186/s13287-021-02624-ypubmed: 34772445google scholar: lookup
        4. Witkowska-Piłaszewicz O, Pingwara R, Winnicka A. The Effect of Physical Training on Peripheral Blood Mononuclear Cell Ex Vivo Proliferation, Differentiation, Activity, and Reactive Oxygen Species Production in Racehorses.. Antioxidants (Basel) 2020 Nov 20;9(11).
          doi: 10.3390/antiox9111155pubmed: 33233549google scholar: lookup
        5. Hu Y, Qi W, Sun L, Zhou H, Zhou B, Yang Z. Effect of TGF-β1 on blood CD4(+)CD25(high) regulatory T cell proliferation and Foxp3 expression during non-small cell lung cancer blood metastasis.. Exp Ther Med 2018 Aug;16(2):1403-1410.
          doi: 10.3892/etm.2018.6306pubmed: 30112067google scholar: lookup
        6. Wilson AD, Hicks C. Both tumour cells and infiltrating T-cells in equine sarcoids express FOXP3 associated with an immune-supressed cytokine microenvironment.. Vet Res 2016 May 9;47(1):55.
          doi: 10.1186/s13567-016-0339-8pubmed: 27160146google scholar: lookup
        7. Hamza E, Mirkovitch J, Steinbach F, Marti E. Regulatory T cells in early life: comparative study of CD4+CD25high T cells from foals and adult horses.. PLoS One 2015;10(3):e0120661.
          doi: 10.1371/journal.pone.0120661pubmed: 25790481google scholar: lookup
        8. Cavatorta DJ, Erb HN, Felippe MJ. Activation-induced FoxP3 expression regulates cytokine production in conventional T cells stimulated with autologous dendritic cells.. Clin Vaccine Immunol 2012 Oct;19(10):1583-92.
          doi: 10.1128/CVI.00308-12pubmed: 22855393google scholar: lookup
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