FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
The International journal of developmental biology2009; 54(2-3); 445-455; doi: 10.1387/ijdb.082795ad

Split immunological tolerance to trophoblast.

Abstract: 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-pregnant mares. Here, we compared the distribution of the major lymphocyte subsets, the percentage of lymphocytes expressing Interferon Gamma (IFNG) and Interleukin 4 (IL4) and the level of expression of the immunoregulatory transcription factor FOXP3 between pregnant and non-pregnant mares, and between peripheral blood and the endometrium during pregnancy. In a cohort of mares in which peripheral blood lymphocytes were tested during early pregnancy and in the non-pregnant state, there were only slight changes observed during pregnancy. In contrast, comparison of peripheral blood lymphocytes with lymphocytes isolated from the endometrial cups of pregnant mares revealed striking differences in lymphocyte sub-populations. The endometrial cups contained higher numbers of IFNG+ lymphocytes, and lower numbers of lymphocytes expressing IL4. The endometrial cup lymphocytes also had higher numbers of FOXP3+ cells compared to peripheral blood lymphocytes. Taken together, these results strengthen the evidence for a state of split tolerance to trophoblast, and furthermore define sharp differences in immune reactivity during equine pregnancy between peripheral blood lymphocytes and lymphocytes at the maternal-fetal interface.
Get Full Text
Publication Date: 2009-10-31 PubMed ID: 19876828PubMed Central: PMC2879498DOI: 10.1387/ijdb.082795adGoogle Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't

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.

The research paper delves into the study of split immunological tolerance to trophoblasts, particularly in pregnant horses or mares. It uncovers how pregnant horses can have strong immune responses to certain foreign antigens, yet show tolerance toward the same antigens in other aspects. By comparing the lymphocyte distribution and expression in pregnant and non-pregnant horses, contrasting findings were discovered, suggesting a state of split tolerance and significant differences in immune reactivity during pregnancy.

Details of the Experiment

  • The study focused on how a pregnant mare’s immune system responds to paternal major histocompatibility complex class I antigens. It discovered that while antibody responses were strong, the anti-paternal cytotoxic T cell responses were comparatively weaker.
  • Researchers compared the major lymphocyte subsets, the percentage of lymphocytes expressing Interferon Gamma (IFNG) and Interleukin 4 (IL4), and the level of expression of the immunoregulatory transcription factor FOXP3 between pregnant and non-pregnant mares.
  • The comparison was also done between peripheral blood and the endometrium or the lining of the uterus of a mare during pregnancy.
  • Lymphocytes were tested during early pregnancy and in the non-pregnant state for the comparisons.

Major Discoveries of the Study

  • There were only small changes observed during pregnancy when the peripheral blood lymphocytes were tested during early pregnancy and in a non-pregnant state.
  • A significant contrast was observed when researchers compared peripheral blood lymphocytes with the ones isolated from the endometrial cups of pregnant mares. There were striking differences in lymphocyte sub-populations in this scenario.
  • The endometrial cups contained higher numbers of IFNG+ lymphocytes, and lower numbers of lymphocytes expressing IL4.
  • Furthermore, the endometrial cup lymphocytes also had higher numbers of FOXP3+ cells compared to peripheral blood lymphocytes.

Implications of the Research

  • The results of this research strongly evidence a state of split tolerance to trophoblast in equine pregnancy.
  • It also highlights that there are distinct differences in immune reactivity during equine pregnancy between peripheral blood lymphocytes and lymphocytes at the maternal-fetal interface.

Cite This Article

APA
de Mestre A, Noronha L, Wagner B, Antczak DF. (2009). Split immunological tolerance to trophoblast. Int J Dev Biol, 54(2-3), 445-455. https://doi.org/10.1387/ijdb.082795ad

Publication

The International journal of developmental biology
ISSN: 1696-3547
NlmUniqueID: 8917470
Country: Spain
Language: English
Volume: 54
Issue: 2-3
Pages: 445-455

Researcher Affiliations

de Mestre, Amanda
  • Department of Veterinary Basic Sciences, The Royal Veterinary College, Royal College Street, London, UK.
Noronha, Leela
    Wagner, Bettina
      Antczak, Douglas F

        MeSH Terms

        • Animals
        • Antibody Formation / immunology
        • Endometrium / immunology
        • Endometrium / metabolism
        • Female
        • Flow Cytometry
        • Forkhead Transcription Factors / genetics
        • Forkhead Transcription Factors / metabolism
        • Histocompatibility Antigens Class I / immunology
        • Histocompatibility Antigens Class I / metabolism
        • Horses
        • Immune Tolerance / immunology
        • Interferon-gamma / metabolism
        • Interleukin-4 / metabolism
        • Organ Specificity / immunology
        • Placenta / immunology
        • Pregnancy
        • RNA, Messenger / genetics
        • RNA, Messenger / metabolism
        • Reverse Transcriptase Polymerase Chain Reaction
        • T-Lymphocytes / immunology
        • T-Lymphocytes / metabolism
        • Trophoblasts / immunology

        Grant Funding

        • R01 HD049545-05 / NICHD NIH HHS
        • R01 HD049545-01 / NICHD NIH HHS
        • R01 HD049545 / NICHD NIH HHS
        • R01-HD049545 / NICHD NIH HHS
        • R01 HD049545-04 / NICHD NIH HHS
        • R01 HD049545-02 / NICHD NIH HHS
        • R01 HD049545-03 / NICHD NIH HHS

        References

        This article includes 71 references
        1. Adams AP, Antczak DF. Ectopic transplantation of equine invasive trophoblast.. Biol Reprod 2001 Mar;64(3):753-63.
          pubmed: 11207188doi: 10.1095/biolreprod64.3.753google scholar: lookup
        2. Adams AP, Oriol JG, Campbell RE, Oppenheim YC, Allen WR, Antczak DF. The effect of skin allografting on the equine endometrial cup reaction.. Theriogenology 2007 Jul 15;68(2):237-47.
          pmc: PMC2259290pubmed: 17559923doi: 10.1016/j.theriogenology.2007.04.058google scholar: lookup
        3. Aït-Azzouzene D, Gendron MC, Houdayer M, Langkopf A, Bürki K, Nemazee D, Kanellopoulos-Langevin C. Maternal B lymphocytes specific for paternal histocompatibility antigens are partially deleted during pregnancy.. J Immunol 1998 Sep 15;161(6):2677-83.
          pubmed: 9743323
        4. Aït-Azzouzene D, Caucheteux S, Tchang F, Wantyghem J, Moutier R, Langkopf A, Gendron MC, Kanellopoulos-Langevin C. Transgenic major histocompatibility complex class I antigen expressed in mouse trophoblast affects maternal immature B cells.. Biol Reprod 2001 Aug;65(2):337-44.
          pubmed: 11466198doi: 10.1095/biolreprod65.2.337google scholar: lookup
        5. Allen WR. Immunological aspects of the equine endometrial cup reaction. 1975. pp. 217–253.
        6. Allen WR. Maternal recognition of pregnancy and immunological implications of trophoblast-endometrium interactions in equids.. Ciba Found Symp 1978;(64):323-52.
          pubmed: 259042doi: 10.1002/9780470720479.ch14google scholar: lookup
        7. Allen WR, Kydd J, Miller J, Antczak DF. Immunological studies on feto-maternal relationships in equine pregnancy. 1984. pp. 183–193.
        8. Aluvihare VR, Kallikourdis M, Betz AG. Regulatory T cells mediate maternal tolerance to the fetus.. Nat Immunol 2004 Mar;5(3):266-71.
          pubmed: 14758358doi: 10.1038/ni1037google scholar: lookup
        9. Antczak DF, Bright SM, Remick LH, Bauman BE. Lymphocyte alloantigens of the horse. I. Serologic and genetic studies.. Tissue Antigens 1982 Sep;20(3):172-87.
          pubmed: 6182639doi: 10.1111/j.1399-0039.1982.tb00343.xgoogle scholar: lookup
        10. Antczak DF, Miller JM, Remick LH. Lymphocyte alloantigens of the horse. II. Antibodies to ELA antigens produced during equine pregnancy.. J Reprod Immunol 1984 Aug;6(5):283-97.
          pubmed: 6481697doi: 10.1016/0165-0378(84)90028-7google scholar: lookup
        11. Antczak DF. Maternal antibody responses in pregnancy.. Curr Opin Immunol 1989 Aug;1(6):1135-40.
          pubmed: 2679750doi: 10.1016/0952-7915(89)90005-8google scholar: lookup
        12. Avelino MM, Campos D Jr, do Carmo Barbosa de Parada J, de Castro AM. Pregnancy as a risk factor for acute toxoplasmosis seroconversion.. Eur J Obstet Gynecol Reprod Biol 2003 May 1;108(1):19-24.
          pubmed: 12694964doi: 10.1016/s0301-2115(02)00353-6google scholar: lookup
        13. Bacon SJ, Ellis SA, Antczak DF. Control of expression of major histocompatibility complex genes in horse trophoblast.. Biol Reprod 2002 Jun;66(6):1612-20.
          pubmed: 12021038doi: 10.1095/biolreprod66.6.1612google scholar: lookup
        14. Baker JM, Bamford AI, Antczak DF. Modulation of allospecific CTL responses during pregnancy in equids: an immunological barrier to interspecies matings?. J Immunol 1999 Apr 15;162(8):4496-501.
          pubmed: 10201987
        15. Baker JM, Bamford AI, Carlson ML, Mcculloch CE, Antczak DF. Equine trophoblast as an immunological target.. J Reprod Fertil Suppl 2000;(56):635-44.
          pubmed: 20681179
        16. Baker RJ, Hernandez-Fuentes MP, Brookes PA, Chaudhry AN, Cook HT, Lechler RI. Loss of direct and maintenance of indirect alloresponses in renal allograft recipients: implications for the pathogenesis of chronic allograft nephropathy.. J Immunol 2001 Dec 15;167(12):7199-206.
          pubmed: 11739543doi: 10.4049/jimmunol.167.12.7199google scholar: lookup
        17. Billington WD. The immunological problem of pregnancy: 50 years with the hope of progress. A tribute to Peter Medawar.. J Reprod Immunol 2003 Oct;60(1):1-11.
          pubmed: 14568673doi: 10.1016/s0165-0378(03)00083-4google scholar: lookup
        18. Blois SM, Ilarregui JM, Tometten M, Garcia M, Orsal AS, Cordo-Russo R, Toscano MA, Bianco GA, Kobelt P, Handjiski B, Tirado I, Markert UR, Klapp BF, Poirier F, Szekeres-Bartho J, Rabinovich GA, Arck PC. A pivotal role for galectin-1 in fetomaternal tolerance.. Nat Med 2007 Dec;13(12):1450-7.
          pubmed: 18026113doi: 10.1038/nm1680google scholar: lookup
        19. Caucheteux SM, Kanellopoulos-Langevin C, Ojcius DM. At the innate frontiers between mother and fetus: linking abortion with complement activation.. Immunity 2003 Feb;18(2):169-72.
          pubmed: 12594944doi: 10.1016/s1074-7613(03)00028-1google scholar: lookup
        20. Chan WF, Razavy H, Luo B, Shapiro AM, Anderson CC. Development of either split tolerance or robust tolerance along with humoral tolerance to donor and third-party alloantigens in nonmyeloablative mixed chimeras.. J Immunol 2008 Apr 15;180(8):5177-86.
          pubmed: 18390699doi: 10.4049/jimmunol.180.8.5177google scholar: lookup
        21. Chung Y, Ko SY, Ko HJ, Kang CY. Split peripheral tolerance: CD40 ligation blocks tolerance induction for CD8 T cells but not for CD4 T cells in response to intestinal antigens.. Eur J Immunol 2005 May;35(5):1381-90.
          pubmed: 15827964doi: 10.1002/eji.200425819google scholar: lookup
        22. de Mestre AM, Khachigian LM, Santiago FS, Staykova MA, Hulett MD. Regulation of inducible heparanase gene transcription in activated T cells by early growth response 1.. J Biol Chem 2003 Dec 12;278(50):50377-85.
          pubmed: 14522979doi: 10.1074/jbc.m310154200google scholar: lookup
        23. de Mestre AM, Bacon SJ, Costa CC, Leadbeater JC, Noronha LE, Stewart F, Antczak DF. Modeling trophoblast differentiation using equine chorionic girdle vesicles.. Placenta 2008 Feb;29(2):158-69.
          pubmed: 18054076doi: 10.1016/j.placenta.2007.10.005google scholar: lookup
        24. Donaldson WL, Zhang CH, Oriol JG, Antczak DF. Invasive equine trophoblast expresses conventional class I major histocompatibility complex antigens.. Development 1990 Sep;110(1):63-71.
          pubmed: 2081471doi: 10.1242/dev.110.1.63google scholar: lookup
        25. Donaldson WL, Oriol JG, Plavin A, Antczak DF. Developmental regulation of class I major histocompatibility complex antigen expression by equine trophoblastic cells.. Differentiation 1992 Dec;52(1):69-78.
          pubmed: 1286777doi: 10.1111/j.1432-0436.1992.tb00501.xgoogle scholar: lookup
        26. Donaldson WL, Oriol JG, Pelkaus CL, Antczak DF. Paternal and maternal major histocompatibility complex class I antigens are expressed co-dominantly by equine trophoblast.. Placenta 1994 Feb-Mar;15(2):123-35.
          pubmed: 8008728doi: 10.1016/s0143-4004(05)80449-7google scholar: lookup
        27. Erlebacher A, Vencato D, Price KA, Zhang D, Glimcher LH. Constraints in antigen presentation severely restrict T cell recognition of the allogeneic fetus.. J Clin Invest 2007 May;117(5):1399-411.
          pmc: PMC1849983pubmed: 17446933doi: 10.1172/jci28214google scholar: lookup
        28. Faas MM, Bouman A, Veenstra van Nieuwenhoven AL, van der Schaaf G, Moes H, Heineman MJ, de Vos P. Species differences in the effect of pregnancy on lymphocyte cytokine production between human and rat.. J Leukoc Biol 2005 Oct;78(4):946-53.
          pubmed: 16033813doi: 10.1189/jlb.0405186google scholar: lookup
        29. Feng G, Wood KJ, Bushell A. Interferon-gamma conditioning ex vivo generates CD25+CD62L+Foxp3+ regulatory T cells that prevent allograft rejection: potential avenues for cellular therapy.. Transplantation 2008 Aug 27;86(4):578-89.
          pubmed: 18724229doi: 10.1097/tp.0b013e3181806a60google scholar: lookup
        30. Flaminio MJ, Antczak DF. Inhibition of lymphocyte proliferation and activation: a mechanism used by equine invasive trophoblast to escape the maternal immune response.. Placenta 2005 Feb-Mar;26(2-3):148-59.
          pubmed: 15708116doi: 10.1016/j.placenta.2004.05.008google scholar: lookup
        31. Flynn L, Carton J, Byrne B, Kelehan P, O'Herlihy C, O'Farrelly C. Optimisation of a technique for isolating lymphocyte subsets from human endometrium.. Immunol Invest 1999 Jul;28(4):235-46.
          pubmed: 10454001doi: 10.3109/08820139909060858google scholar: lookup
        32. Grünig G, Triplett L, Canady LK, Allen WR, Antczak DF. The maternal leucocyte response to the endometrial cups in horses is correlated with the developmental stages of the invasive trophoblast cells.. Placenta 1995 Sep;16(6):539-59.
          pubmed: 8570575doi: 10.1016/s0143-4004(05)80005-0google scholar: lookup
        33. Hunziker RD, Lynch F, Shevach EM, Margulies DH. Split tolerance to the MHC class I molecule H-2Dd in animals transgenic for its soluble analog.. Hum Immunol 1997 Feb;52(2):82-94.
          pubmed: 9077557doi: 10.1016/s0198-8859(96)00287-xgoogle scholar: lookup
        34. Hunt JS. Stranger in a strange land.. Immunol Rev 2006 Oct;213:36-47.
          pmc: PMC1637092pubmed: 16972895doi: 10.1111/j.1600-065x.2006.00436.xgoogle scholar: lookup
        35. Jiang SP, Vacchio MS. Multiple mechanisms of peripheral T cell tolerance to the fetal "allograft".. J Immunol 1998 Apr 1;160(7):3086-90.
          pubmed: 9531261
        36. Kanellopoulos-Langevin C, Caucheteux SM, Verbeke P, Ojcius DM. Tolerance of the fetus by the maternal immune system: role of inflammatory mediators at the feto-maternal interface.. Reprod Biol Endocrinol 2003 Dec 2;1:121.
          pmc: PMC305337pubmed: 14651750doi: 10.1186/1477-7827-1-121google scholar: lookup
        37. Koch CA, Platt JL. Natural mechanisms for evading graft rejection: the fetus as an allograft.. Springer Semin Immunopathol 2003 Sep;25(2):95-117.
          pubmed: 12955462doi: 10.1007/s00281-003-0136-0google scholar: lookup
        38. Krishnan L, Guilbert LJ, Russell AS, Wegmann TG, Mosmann TR, Belosevic M. Pregnancy impairs resistance of C57BL/6 mice to Leishmania major infection and causes decreased antigen-specific IFN-gamma response and increased production of T helper 2 cytokines.. J Immunol 1996 Jan 15;156(2):644-52.
          pubmed: 8543816
        39. Krishnan L, Guilbert LJ, Wegmann TG, Belosevic M, Mosmann TR. T helper 1 response against Leishmania major in pregnant C57BL/6 mice increases implantation failure and fetal resorptions. Correlation with increased IFN-gamma and TNF and reduced IL-10 production by placental cells.. J Immunol 1996 Jan 15;156(2):653-62.
          pubmed: 8543817
        40. Lazary S, Antczak DF, Bailey E, Bell TK, Bernoco D, Byrns G, McClure JJ. Joint Report of the Fifth International Workshop on Lymphocyte Alloantigens of the Horse, Baton Rouge, Louisiana, 31 October-1 November 1987.. Anim Genet 1988;19(4):447-56.
          pubmed: 2466424doi: 10.1111/j.1365-2052.1988.tb00836.xgoogle scholar: lookup
        41. Lunn DP, Holmes MA, Antczak DF, Agerwal N, Baker J, Bendali-Ahcene S, Blanchard-Channell M, Byrne KM, Cannizzo K, Davis W, Hamilton MJ, Hannant D, Kondo T, Kydd JH, Monier MC, Moore PF, O'Neil T, Schram BR, Sheoran A, Stott JL, Sugiura T, Vagnoni KE. Report of the Second Equine Leucocyte Antigen Workshop, Squaw valley, California, July 1995.. Vet Immunol Immunopathol 1998 Mar 31;62(2):101-43.
          pubmed: 9638857doi: 10.1016/s0165-2427(97)00160-8google scholar: lookup
        42. Luo B, Chan WF, Shapiro AM, Anderson CC. Non-myeloablative mixed chimerism approaches and tolerance, a split decision.. Eur J Immunol 2007 May;37(5):1233-42.
          pubmed: 17390394doi: 10.1002/eji.200636938google scholar: lookup
        43. Maher JK, Tresnan DB, Deacon S, Hannah L, Antczak DF. Analysis of MHC class I expression in equine trophoblast cells using in situ hybridization.. Placenta 1996 Jul-Aug;17(5-6):351-9.
          pubmed: 8829219doi: 10.1016/s0143-4004(96)90060-0google scholar: lookup
        44. Mathes DW, Randolph MA, Solari MG, Nazzal JA, Nielsen GP, Arn JS, Sachs DH, Lee WP. Split tolerance to a composite tissue allograft in a swine model.. Transplantation 2003 Jan 15;75(1):25-31.
          pubmed: 12544866doi: 10.1097/00007890-200301150-00005google scholar: lookup
        45. Medawar PB. Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates. Symp. Soc. Exp. Biol. 1953;11:320–338.
        46. Mellor AL, Munn DH. Immunology at the maternal-fetal interface: lessons for T cell tolerance and suppression.. Annu Rev Immunol 2000;18:367-91.
          pubmed: 10837063doi: 10.1146/annurev.immunol.18.1.367google scholar: lookup
        47. Moffett A, Loke C. Immunology of placentation in eutherian mammals.. Nat Rev Immunol 2006 Aug;6(8):584-94.
          pubmed: 16868549doi: 10.1038/nri1897google scholar: lookup
        48. Nagler-Anderson C, Bhan AK, Podolsky DK, Terhorst C. Control freaks: immune regulatory cells.. Nat Immunol 2004 Feb;5(2):119-22.
          pubmed: 14749778doi: 10.1038/ni0204-119google scholar: lookup
        49. Oliveira LJ, Hansen PJ. Deviations in populations of peripheral blood mononuclear cells and endometrial macrophages in the cow during pregnancy.. Reproduction 2008 Oct;136(4):481-90.
          pubmed: 18635742doi: 10.1530/rep-08-0218google scholar: lookup
        50. Pejcic-Karapetrovic B, Gurnani K, Russell MS, Finlay BB, Sad S, Krishnan L. Pregnancy impairs the innate immune resistance to Salmonella typhimurium leading to rapid fatal infection.. J Immunol 2007 Nov 1;179(9):6088-96.
          pubmed: 17947683doi: 10.4049/jimmunol.179.9.6088google scholar: lookup
        51. Qian S, Lu L, Li Y, Fu F, Li W, Starzl TE, Thomson AW, Fung JJ. Apoptosis of graft-infiltrating cytotoxic T cells: a mechanism underlying "split tolerance" in mouse liver transplantation.. Transplant Proc 1997 Feb-Mar;29(1-2):1168-9.
          pmc: PMC2955444pubmed: 9123257doi: 10.1016/s0041-1345(96)00521-0google scholar: lookup
        52. Ramsdell F. Foxp3 and natural regulatory T cells: key to a cell lineage?. Immunity 2003 Aug;19(2):165-8.
          pubmed: 12932350doi: 10.1016/s1074-7613(03)00207-3google scholar: lookup
        53. Robertson SA, Mau VJ, Hudson SN, Tremellen KP. Cytokine-leukocyte networks and the establishment of pregnancy.. Am J Reprod Immunol 1997 Jun;37(6):438-42.
          pubmed: 9228299doi: 10.1111/j.1600-0897.1997.tb00257.xgoogle scholar: lookup
        54. Robertson SA, Sharkey DJ. The role of semen in induction of maternal immune tolerance to pregnancy.. Semin Immunol 2001 Aug;13(4):243-54.
          pubmed: 11437632doi: 10.1006/smim.2000.0320google scholar: lookup
        55. Saito S, Sasaki Y, Sakai M. CD4(+)CD25high regulatory T cells in human pregnancy.. J Reprod Immunol 2005 Apr;65(2):111-20.
          pubmed: 15811516doi: 10.1016/j.jri.2005.01.004google scholar: lookup
        56. Sasaki Y, Darmochwal-Kolarz D, Suzuki D, Sakai M, Ito M, Shima T, Shiozaki A, Rolinski J, Saito S. Proportion of peripheral blood and decidual CD4(+) CD25(bright) regulatory T cells in pre-eclampsia.. Clin Exp Immunol 2007 Jul;149(1):139-45.
          pmc: PMC1942015pubmed: 17459078doi: 10.1111/j.1365-2249.2007.03397.xgoogle scholar: lookup
        57. Scaife PJ, Bulmer JN, Robson SC, Innes BA, Searle RF. Effector activity of decidual CD8+ T lymphocytes in early human pregnancy.. Biol Reprod 2006 Oct;75(4):562-7.
          pubmed: 16822900doi: 10.1095/biolreprod.106.052654google scholar: lookup
        58. Seavey MM, Mosmann TR. Immunoregulation of fetal and anti-paternal immune responses.. Immunol Res 2008;40(2):97-113.
          pubmed: 18213524doi: 10.1007/s12026-007-8005-xgoogle scholar: lookup
        59. Somerset DA, Zheng Y, Kilby MD, Sansom DM, Drayson MT. Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T-cell subset.. Immunology 2004 May;112(1):38-43.
          pmc: PMC1782465pubmed: 15096182doi: 10.1111/j.1365-2567.2004.01869.xgoogle scholar: lookup
        60. Sprent J, Hurd M, Schaefer M, Heath W. Split tolerance in spleen chimeras.. J Immunol 1995 Feb 1;154(3):1198-206.
          pubmed: 7822792
        61. Smith JL. Foodborne infections during pregnancy.. J Food Prot 1999 Jul;62(7):818-29.
          pubmed: 10419281doi: 10.4315/0362-028x-62.7.818google scholar: lookup
        62. Tafuri A, Alferink J, Möller P, Hämmerling GJ, Arnold B. T cell awareness of paternal alloantigens during pregnancy.. Science 1995 Oct 27;270(5236):630-3.
          pubmed: 7570020doi: 10.1126/science.270.5236.630google scholar: lookup
        63. Tilburgs T, Roelen DL, van der Mast BJ, van Schip JJ, Kleijburg C, de Groot-Swings GM, Kanhai HH, Claas FH, Scherjon SA. Differential distribution of CD4(+)CD25(bright) and CD8(+)CD28(-) T-cells in decidua and maternal blood during human pregnancy.. Placenta 2006 Apr;27 Suppl A:S47-53.
          pubmed: 16442616doi: 10.1016/j.placenta.2005.11.008google scholar: lookup
        64. Tilburgs T, Roelen DL, van der Mast BJ, de Groot-Swings GM, Kleijburg C, Scherjon SA, Claas FH. Evidence for a selective migration of fetus-specific CD4+CD25bright regulatory T cells from the peripheral blood to the decidua in human pregnancy.. J Immunol 2008 Apr 15;180(8):5737-45.
          pubmed: 18390759doi: 10.4049/jimmunol.180.8.5737google scholar: lookup
        65. Trowsdale J, Betz AG. Mother's little helpers: mechanisms of maternal-fetal tolerance.. Nat Immunol 2006 Mar;7(3):241-6.
          pubmed: 16482172doi: 10.1038/ni1317google scholar: lookup
        66. Wagner B, Robeson J, McCracken M, Wattrang E, Antczak DF. Horse cytokine/IgG fusion proteins--mammalian expression of biologically active cytokines and a system to verify antibody specificity to equine cytokines.. Vet Immunol Immunopathol 2005 May 1;105(1-2):1-14.
          pubmed: 15797470doi: 10.1016/j.vetimm.2004.11.010google scholar: lookup
        67. Wagner B, Hillegas JM, Antczak DF. A monoclonal antibody to equine interleukin-4.. Vet Immunol Immunopathol 2006 Apr 15;110(3-4):363-7.
          pubmed: 16480777doi: 10.1016/j.vetimm.2006.01.001google scholar: lookup
        68. Wagner B, Hillegas JM, Brinker DR, Horohov DW, Antczak DF. Characterization of monoclonal antibodies to equine interleukin-10 and detection of T regulatory 1 cells in horses.. Vet Immunol Immunopathol 2008 Mar 15;122(1-2):57-64.
          pubmed: 18061278doi: 10.1016/j.vetimm.2007.10.012google scholar: lookup
        69. Wood KJ, Sakaguchi S. Regulatory T cells in transplantation tolerance.. Nat Rev Immunol 2003 Mar;3(3):199-210.
          pubmed: 12658268doi: 10.1038/nri1027google scholar: lookup
        70. Zenclussen AC, Schumacher A, Zenclussen ML, Wafula P, Volk HD. Immunology of pregnancy: cellular mechanisms allowing fetal survival within the maternal uterus.. Expert Rev Mol Med 2007 Apr 27;9(10):1-14.
          pubmed: 17462112doi: 10.1017/s1462399407000294google scholar: lookup
        71. Zenclussen AC, Gerlof K, Zenclussen ML, Ritschel S, Zambon Bertoja A, Fest S, Hontsu S, Ueha S, Matsushima K, Leber J, Volk HD. Regulatory T cells induce a privileged tolerant microenvironment at the fetal-maternal interface.. Eur J Immunol 2006 Jan;36(1):82-94.
          pubmed: 16358362doi: 10.1002/eji.200535428google scholar: lookup

        Citations

        This article has been cited 24 times.
        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. Murrieta-Coxca JM, Fuentes-Zacarias P, Ospina-Prieto S, Markert UR, Morales-Prieto DM. Synergies of Extracellular Vesicles and Microchimerism in Promoting Immunotolerance During Pregnancy. Front Immunol 2022;13:837281.
          doi: 10.3389/fimmu.2022.837281pubmed: 35844513google scholar: lookup
        3. Tavares Pereira M, Nowaczyk R, Aslan S, Ay SS, Kowalewski MP. Utero-Placental Immune Milieu during Normal and Aglepristone-Induced Parturition in the Dog. Animals (Basel) 2021 Dec 19;11(12).
          doi: 10.3390/ani11123598pubmed: 34944375google scholar: lookup
        4. Antczak DF, Allen WRT. Placentation in Equids. Adv Anat Embryol Cell Biol 2021;234:91-128.
          doi: 10.1007/978-3-030-77360-1_6pubmed: 34694479google scholar: lookup
        5. Buska-Mach K, Kedzierska AE, Lepczynski A, Herosimczyk A, Ozgo M, Karpinski P, Gomulkiewicz A, Lorek D, Slawek A, Dziegiel P, Chelmonska-Soyta A. Differential Signals From TNFα-Treated and Untreated Embryos in Uterine Tissues and Splenic CD4(+) T Lymphocytes During Preimplantation Pregnancy in Mice. Front Vet Sci 2021;8:641553.
          doi: 10.3389/fvets.2021.641553pubmed: 33763465google scholar: lookup
        6. Lee SJ, Kim HJ, Byun NR, Park CG. Donor-Specific Regulatory T Cell-Mediated Immune Tolerance in an Intrahepatic Murine Allogeneic Islet Transplantation Model with Short-Term Anti-CD154 mAb Single Treatment. Cell Transplant 2020 Jan-Dec;29:963689720913876.
          doi: 10.1177/0963689720913876pubmed: 32216448google scholar: lookup
        7. Read JE, Cabrera-Sharp V, Offord V, Mirczuk SM, Allen SP, Fowkes RC, de Mestre AM. Dynamic changes in gene expression and signalling during trophoblast development in the horse. Reproduction 2018 Oct 1;156(4):313–330.
          doi: 10.1530/REP-18-0270pubmed: 30306765google scholar: lookup
        8. Read JE, Cabrera-Sharp V, Offord V, Mirczuk SM, Allen SP, Fowkes RC, de Mestre AM. Dynamic changes in gene expression and signalling during trophoblast development in the horse. Reproduction 2018 Oct 1;156(4):313-330.
          doi: 10.1530/REP-18-0270pubmed: 29991567google scholar: lookup
        9. Krakowski L, Bartoszek P, Krakowska I, Stachurska A, Piech T, Brodzki P, Wrona Z. Changes in Blood Lymphocyte Subpopulations and Expression of MHC-II Molecules in Wild Mares Before and After Parturition. J Vet Res 2017 Jun;61(2):217-221.
          doi: 10.1515/jvetres-2017-0028pubmed: 29978076google scholar: lookup
        10. Brosnahan MM, Silvela EJ, Crumb J, Miller DC, Erb HN, Antczak DF. Ectopic Trophoblast Allografts in the Horse Resist Destruction by Secondary Immune Responses. Biol Reprod 2016 Dec;95(6):135.
          doi: 10.1095/biolreprod.115.137851pubmed: 27760752google scholar: lookup
        11. Antczak DF, de Mestre AM, Wilsher S, Allen WR. The equine endometrial cup reaction: a fetomaternal signal of significance. Annu Rev Anim Biosci 2013 Jan;1:419-42.
          doi: 10.1146/annurev-animal-031412-103703pubmed: 25387026google scholar: lookup
        12. Rapacz-Leonard A, Dąbrowska M, Janowski T. Major histocompatibility complex I mediates immunological tolerance of the trophoblast during pregnancy and may mediate rejection during parturition. Mediators Inflamm 2014;2014:579279.
          doi: 10.1155/2014/579279pubmed: 24812442google scholar: lookup
        13. Maj T, Slawek A, Chelmonska-Soyta A. CD80 and CD86 costimulatory molecules differentially regulate OT-II CD4⁺ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. Mediators Inflamm 2014;2014:769239.
          doi: 10.1155/2014/769239pubmed: 24771983google scholar: lookup
        14. Oliveira LJ, Mansouri-Attia N, Fahey AG, Browne J, Forde N, Roche JF, Lonergan P, Fair T. Characterization of the Th profile of the bovine endometrium during the oestrous cycle and early pregnancy. PLoS One 2013;8(10):e75571.
          doi: 10.1371/journal.pone.0075571pubmed: 24204576google scholar: lookup
        15. Noronha LE, Harman RM, Wagner B, Antczak DF. Generation and characterization of monoclonal antibodies to equine NKp46. Vet Immunol Immunopathol 2012 Jun 15;147(1-2):60-8.
          doi: 10.1016/j.vetimm.2012.04.003pubmed: 22551980google scholar: lookup
        16. Brosnahan MM, Miller DC, Adams M, Antczak DF. IL-22 is expressed by the invasive trophoblast of the equine (Equus caballus) chorionic girdle. J Immunol 2012 May 1;188(9):4181-7.
          doi: 10.4049/jimmunol.1103509pubmed: 22490443google scholar: lookup
        17. Noronha LE, Harman RM, Wagner B, Antczak DF. Generation and characterization of monoclonal antibodies to equine CD16. Vet Immunol Immunopathol 2012 Apr 15;146(2):135-42.
          doi: 10.1016/j.vetimm.2012.02.006pubmed: 22424928google scholar: lookup
        18. Noronha LE, Huggler KE, de Mestre AM, Miller DC, Antczak DF. Molecular evidence for natural killer-like cells in equine endometrial cups. Placenta 2012 May;33(5):379-86.
          doi: 10.1016/j.placenta.2012.01.018pubmed: 22357194google scholar: lookup
        19. de Mestre AM, Hanlon D, Adams AP, Runcan E, Leadbeater JC, Erb HN, Costa CC, Miller D, Allen WR, Antczak DF. Functions of ectopically transplanted invasive horse trophoblast. Reproduction 2011 Jun;141(6):849-56.
          doi: 10.1530/REP-10-0462pubmed: 21389079google scholar: lookup
        20. Wagner B, Burton A, Ainsworth D. Interferon-gamma, interleukin-4 and interleukin-10 production by T helper cells reveals intact Th1 and regulatory TR1 cell activation and a delay of the Th2 cell response in equine neonates and foals. Vet Res 2010 Jul-Aug;41(4):47.
          doi: 10.1051/vetres/2010019pubmed: 20374696google scholar: lookup
        21. Van de Walle GR, Harman RM. Contributions of large and agricultural animal models to immunology. J Immunol 2025 Oct 1;214(10):2494-2503.
          doi: 10.1093/jimmun/vkaf119pubmed: 41169229google scholar: lookup
        22. Satué K, La Fauci D, Medica P, Damiá Gímenez E, Cravana C, Fazio E. Shifts between pro-inflammatory and anti-inflammatory profiles in pregnant mares: a review of physiological functions. Front Vet Sci 2025;12:1660759.
          doi: 10.3389/fvets.2025.1660759pubmed: 41049139google scholar: lookup
        23. Carter AM. Evolution of Placental Hormones: Implications for Animal Models. Front Endocrinol (Lausanne) 2022;13:891927.
          doi: 10.3389/fendo.2022.891927pubmed: 35692413google scholar: lookup
        24. Kammerer R, Ballesteros A, Bonsor D, Warren J, Williams JM, Moore T, Dveksler G. Equine pregnancy-specific glycoprotein CEACAM49 secreted by endometrial cup cells activates TGFB. Reproduction 2020 Nov;160(5):685-694.
          doi: 10.1530/REP-20-0277pubmed: 33065543google scholar: lookup
        Subscribe to our newsletter
        Join 99,727 horse owners like you who receive our email updates on horse health and nutrition.