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착상과 임신 초기 면역반응에서 T 림프구의 역할
Roles of T Lymphocytes in Early Human Reproduction

양광문   (관동대학교 의과대학  );
  • 초록

    착상, 태반생성 및 임신 유지 등 생식과정에서 semi-allograft인 배아 및 태아가 생존하기 위해서는 모체 면역계의 면역관용이 요구된다. 면역관용은 분자 생물학적으로 염증반응과 항염증반응의 적절한 균형을 유지하는 인식되고 있으며, 생식과정에서 모체 면역계의 T 림프구, 자연살해세포, 수지상 세포, 대식세포 등 여러 면역세포의 유기적인 협조하에 이루어진다. 면역세포들은 특정 항원 및 사이토카인의 자극에 따라 정반대의 성질을 가진 사이토카인을 생산, 분비할 수 있는 특성을 가지고 있어 각각을 염증성 또는 항염증성 면역세포로 명확히 구분할 수 없으며 면역세포의 이러한 특성에 의해 생산 및 분비되는 사이토카인의 종류에 따라 Th0 형 (Th 0 cell, Tc 0 cell, NK 0 cell), Th1형 (Th 1 cell, Tc 1 cell, NK 1 cell), Th2 형 (Th 2 cell, Tc 2 cell, NK 2 cell), Th3 형 세포 (Th 3 cell, Tc 3 cell, NK 3 cell)로 분류하기도 한다. 즉, 착상 시기에 혈관신생 및 영양막의 자궁 내 침투를 위한 적절한 염증성 사이토카인(inflammatory cytokine)의 분비 및 임신의 지속을 위한 항염증성 (anti-inflammatory) 사이토카인의 분비 등 생식과정에서 수반되는 염증성과 항염증성 면역반응의 적절한 균형을 유지하는 기전은 특정 면역세포만의 작용으로 결론 지을 수 없으며 면역 세포간 network의 산물이라 할 수 있다 (Figure 5). 면역세포 중 최근 그 존재가 알려진 면역조절 T림프구 (T reg cell)는 여러 연구자들에 의해 면역관용에 관여함이 일관되게 보고되고 있어 자궁 내모체-태아간 접촉면에서 면역세포들 간의 network에 중추적인 역할을 할 것으로 인식되고 있으나 작용기전으로 제시되고 있는 가설들을 뒷받침 할 만한 객관적인 연구가 필요한 실정이다. 본 고찰에서는 착상과 임신 유지 등 생식과정에 수반되는 면역세포 및 그 세포들의 작용기전중 T 림프구의 역할에 중점을 두고 그 분류 및 기능에 대해 정리해 보았다. 결론적으로 착상과 임신의 유지 등 생식과정에서 T 림프구는 면역관용과 거부에 적극적으로 작용하며 착상부전, 습관성유산 등 면역학적 병인이 유사한 생식장애 (poor reproductive performance)들의 발병에 중요한 역할을 하는 것은 의심할 여지가 없다. 하지만 향후 T 림프구 및 그와 연관된 면역세포들의 작용에 대한 확실한 분자학적 규명이 요구된다.


  • 참고문헌 (66)

    1. Billingham RE, Brent L, Medawar PB. Actively acquired tolerance of foreign cells. Nature 1953; 172: 603-6 
    2. Hunt JS, Petroff MG, McIntire RH, Ober C. HLA-G and immune tolerance in pregnancy. FASEB J 2005; 19: 681-93 
    3. Xu C, Mao D, Holers VM, Palanca B, Cheng AM, Molina H. A critical role for murine complement regulator crry in fetomaternal tolerance. Science 2000; 287: 498-501 
    4. Dong M, Ding G, Zhou J, Wang H, Zhao Y, Huang H. The effect of trophoblasts on T lymphocytes: possible regulatory effector molecules--a proteomic analysis. Cell Physiol Biochem 2008; 21: 463-72 
    5. Lachapelle MH, Miron P, Hemmings R, Roy DC. Endometrial T, B, and NK cells in patients with recurrent spontaneous abortion. Altered profile and pregnancy outcome. J Immunol 1996; 156: 4027-34 
    6. Quack KC, Vassiliadou N, Pudney J, Anderson DJ, Hill JA. Leukocyte activation in the decidua of chromosomally normal and abnormal fetuses from women with recurrent abortion. Hum Reprod 2001; 16: 949-55 
    7. Fallarino F, Grohmann U, Hwang KW, et al. Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 2003; 4: 1206-12 
    8. Mellor AL, Munn DH. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 2004; 4: 762-74 
    9. Fraccaroli L, Alfieri J, Larocca L, et al. A potential tolerogenic immune mechanism in a trophoblast cell line through the activation of chemokine-induced T cell death and regulatory T cell modulation. Hum Reprod 2009; 24(1):166-75 
    10. Boyson JE, Nagarkatti N, Nizam L, Exley MA, Strominger JL. Gestation stage-dependent mechanisms of invariant natural killer T cell-mediated pregnancy loss. Proc Natl Acad Sci U S A 2006; 103: 4580-5 
    11. Nagarajan NA, Kronenberg M. Invariant NKT cells amplify the innate immune response to lipopolysaccharide. J Immunol 2007; 178: 2706-13 
    12. Jonuleit H, Schmitt E. The regulatory T cell family: distinct subsets and their interrelations. J Immunol 2003; 171: 6323-7 
    13. Ingman WV, Robker RL, Woittiez K, Robertson SA. Null mutation in transforming growth factor beta1 disrupts ovarian function and causes oocyte incompetence and early embryo arrest. Endocrinology 2006; 147: 835-45 
    14. Ntrivalas E, Kwak-Kim J, Beaman K, Mantouvalos H, Gilman-Sachs A. An in vitro coculture model to study cytokine profiles of natural killer cells during maternal immune celltrophoblast interactions. J Soc Gynecol Investig 2006; 13: 196-202 
    15. Arslan E, Colakoglu M, Celik C, et al. Serum TNF-alpha, IL-6, lupus anticoagulant and anticardiolipin antibody in women with and without a past history of recurrent miscarriage. Arch Gynecol Obstet 2004; 270: 227-9 
    16. Johnson PM, Christmas SE, Vince GS. Immunological aspects of implantation and implantation failure. Hum Reprod 1999; 14 Suppl 2: 26-36 
    17. Athanassakis I, Bleackley RC, Paetkau V, Guilbert L, Barr PJ, Wegmann TG. The immunostimulatory effect of T cells and T cell lymphokines on murine fetally derived placental cells. J Immunol 1987; 138: 37-44 
    18. Clark DA. Controversies in reproductive immunology. Crit Rev Immunol 1991; 11: 215-47 
    19. Aschkenazi S, Straszewski S, Verwer KMA, Foellmer H, Rutherford T, Mor G. Differential Regulation and Function of the Fas/Fas Ligand System in Human Trophoblast Cells. Biol Reprod 2002; 66: 1853-1861 
    20. Bulmer JN, Morrison L, Longfellow M, Ritson A, Pace D. Granulated lymphocytes in human endometrium: histochemical and immunohistochemical studies. Hum Reprod 1991; 6: 791-8 
    21. Barakonyi A, Polgar B, Szekeres-Bartho J. The role of gamma/delta T-cell receptor-positive cells in pregnancy: part II. Am J Reprod Immunol 1999; 42: 83-7 
    22. Arck PC, Ferrick DA, Steele-Norwood D, et al. Murine T cell determination of pregnancy outcome. Cell Immunol 1999; 196: 71-9 
    23. Wilczynski JR. Immunological analogy between allograft rejection, recurrent abortion and pre-eclampsia - the same basic mechanism? Hum Immunol 2006; 67: 492-511 
    24. Guleria I, Khosroshahi A, Ansari MJ, et al. A critical role for the programmed death ligand 1 in fetomaternal tolerance. J Exp Med 2005; 202: 231-7 
    25. Sacks GP, Clover LM, Bainbridge DR, Redman CW, Sargent IL. Flow cytometric measurement of intracellular Th1 and Th2 cytokine production by human villous and extravillous cytotrophoblast. Placenta 2001; 22: 550-9 
    26. Kwak-Kim J, Yang KM, Gilman-Sachs A. Recurrent pregnancy loss: A disease of inflammation and coagulation. J Obstet Gynaecol Res 2009; 35: 609-22 
    27. Piccirillo CA, Shevach EM. Naturally-occurring CD4+CD25+ immunoregulatory T cells: central players in the arena of peripheral tolerance. Semin Immunol 2004; 16: 81-8 
    28. Piccinni MP, Bani D, Beloni L, et al. Relaxin favors the development of activated human T cells into Th1-like effectors. Eur J Immunol 1999; 29: 2241-7 
    29. Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today 1993; 14: 353-6 
    30. Wu L, Wu Y, Gathings B, et al. Smad4 as a transcription corepressor for estrogen receptor alpha. J Biol Chem 2003; 278: 15192-200 
    31. Eberl G, MacDonald HR. Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells. Eur J Immunol 2000; 30: 985-92 
    32. Piccini MP. T-cell cytokines in pregnancy. Am J Reprod Immunol 2002; 47: 289-94 
    33. Yahata T, Kurabayashi T, Honda A, Takakuwa K, Tanaka K, Abo T. Decrease in the proportion of granulated CD56+ T-cells in patients with a history of recurrent abortion. J Reprod Immunol 1998; 38: 63-73 
    34. White CA, Johansson M, Roberts CT, Ramsay AJ, Robertson SA. Effect of interleukin-10 null mutation on maternal immune response and reproductive outcome in mice. Biol Reprod 2004; 70: 123-31 
    35. Shi Y, Ling B, Zhou Y, et al. Interferon-gamma expression in natural killer cells and natural killer T cells is suppressed in early pregnancy. Cell Mol Immunol 2007; 4: 389-94 
    36. Vassilidou N, Bulmer JN. Quantitative analysis of T lymphocyte subsets in pregnant and nonpregnant human endometrium. Biol Reprod 1996; 55: 1017-22 
    37. Chaplin DD. 1. Overview of the immune response. J Allergy Clin Immunol 2003; 111: S442-59 
    38. Arruvito L, Sanz M, Banham AH, Fainboim L. Expansion of CD4+CD25+ and FOXP3+ regulatory T cells during the follicular phase of the menstrual cycle: implications for human reproduction. J Immunol 2007; 178: 2572-8 
    39. Boyson JE, Aktan I, Barkhuff DA, Chant A. NKT cells at the maternal-fetal interface. Immunol Invest 2008; 37: 565-82 
    40. Clark DA, Merali FS, Hoskin DW, et al. Decidua-associated suppressor cells in abortion-prone DBA/2-mated CBA/J mice that release bioactive transforming growth factor beta2-related immunosuppressive molecules express a bone marrow-derived natural suppressor cell marker and gamma delta T-cell receptor. Biol Reprod 1997; 56: 1351-60 
    41. Szekeres-Bartho J, Barakonyi A, Miko E, Polgar B, Palkovics T. The role of gamma/delta T cells in the feto-maternal relationship. Semin Immunol 2001; 13: 229-33 
    42. Piccinni MP, Giudizi MG, Biagiotti R, et al. Progesterone favors the development of human T helper cells producing Th2-type cytokines and promotes both IL-4 production and membrane CD30 expression in established Th1 cell clones. J Immunol 1995; 155: 128-33 
    43. Groux H, O'Garra A, Bigler M, et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997; 389: 737-42 
    44. Ito K, Karasawa M, Kawano T, et al. Involvement of decidual Valpha14 NKT cells in abortion. Proc Natl Acad Sci U S A 2000; 97: 740-4 
    45. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989; 7: 145-73 
    46. Raghupathy R. Pregnancy: success and failure within the Th1/Th2/Th3 paradigm. Semin Immunol 2001; 13: 219-27 
    47. Groux H. An overview of regulatory T cells. Microbes Infect 2001; 3: 883-9 
    48. Rezaei A, Dabbagh A. T-helper (1) cytokines increase during early pregnancy in women with a history of recurrent spontaneous abortion. Med Sci Monit 2002; 8: CR607-10 
    49. Straub RH. The complex role of estrogens in inflammation. Endocr Rev 2007; 28: 521-74 
    50. Bluestone JA, Abbas AK. Natural versus adaptive regulatory T cells. Nat Rev Immunol 2003; 3: 253-7 
    51. Yamamoto T, Takahashi Y, Kase N, Mori H. Role of decidual natural killer (NK) cells in patients with missed abortion: differences between cases with normal and abnormal chromosome. Clin Exp Immunol 1999; 116: 449-52 
    52. Saito S, Sasaki Y, Sakai M. CD4(+)CD25high regulatory T cells in human pregnancy. J Reprod Immunol 2005; 65: 111-20 
    53. Boyson JE, Rybalov B, Koopman LA, et al. CD1d and invariant NKT cells at the human maternal-fetal interface. Proc Natl Acad Sci U S A 2002; 99: 13741-6 
    54. Fukaura H, Kent SC, Pietrusewicz MJ, Khoury SJ, Weiner HL, Hafler DA. Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factorbeta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients. J Clin Invest 1996; 98: 70-7 
    55. Bennett WA, Lagoo-Deenadayalan S, Whitorth NS, et al. Firsttrimester human chorionic villi express both immunoregulatory and inflammatory cytokines: a role for interleukin-10 in regulating the cytokine network of pregnancy. Am J Reprod Immunol 1999; 41: 70-8 
    56. Aluvihare VR, Kallikourdis M, Betz AG. Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 2004; 5: 266-71 
    57. Raghupathy R, Makhseed M, Azizieh F, Hassan N, Al-Azemi M, Al-Shamali E. Maternal Th1- and Th2-type reactivity to placental antigens in normal human pregnancy and unexplained recurrent spontaneous abortions. Cell Immunol 1999; 196: 122-30 
    58. Guerin LR, Prins JR, Robertson SA. Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment? Hum Reprod Update 2009; 15: 517-35 
    59. Chaouat G, Menu E, Athanassakis I, Wegmann TG. Maternal T cells regulate placental size and fetal survival. Reg Immunol 1988; 1: 143-8 
    60. Bustos D, Moret A, Tambutti M, et al. Autoantibodies in Argentine women with recurrent pregnancy loss. Am J Reprod Immunol 2006; 55: 201-7 
    61. Weiner HL. Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol Rev 2001; 182: 207-14 
    62. Kwak-Kim JY, Chung-Bang HS, Ng SC, et al. Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF. Hum Reprod 2003; 18: 767-73 
    63. Mellor AL, Sivakumar J, Chandler P, et al. Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nat Immunol 2001; 2: 64-8 
    64. Kawano T, Cui J, Koezuka Y, et al. CD1d-restricted and TCRmediated activation of valpha14 NKT cells by glycosylceramides. Science 1997; 278: 1626-9 
    65. Chaouat G, Menu E, Clark DA, Dy M, Minkowski M, Wegmann TG. Control of fetal survival in CBA $\times$ DBA/2 mice by lymphokine therapy. J Reprod Fertil 1990; 89: 447-58 
    66. Makhseed M, Raghupathy R, Azizieh F, Farhat R, Hassan N, Bandar A. Circulating cytokines and CD30 in normal human pregnancy and recurrent spontaneous abortions. Hum Reprod 2000; 15: 2011-7 

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