Molecular Human Reproduction · 2004 · 736 citations · 23 references
Lymphocyte DevelopmentT-regulatory CellImmunologyReproductive HealthGynecologyT CellsEarly Pregnancy SubjectsHuman PregnancyMaternal ImmunizationDecidual Cd4Public HealthCell TransplantationInfertilityMaternal HealthAutoimmunitySelf-toleranceTolerance InductionCell BiologySpontaneous Abortion CasesAbortionPregnancyCellular Immune ResponseMedicineCell Development
Human pregnancy is a semi‑allograft that depends on immune tolerance mechanisms, yet the specific role of CD4⁺CD25^bright regulatory T cells in this tolerance has not been previously described. We found that decidual CD4⁺CD25^bright T cells, which express high levels of CTLA‑4, potently suppress autologous T‑cell proliferation in a cell‑contact–dependent, dose‑dependent manner, and their reduced frequency in spontaneous abortion samples implicates them in sustaining maternal immune tolerance and pregnancy.
Human pregnancy represents a situation of semiallograft to maternal host. Therefore, it has been reported that tolerance to the fetal allograft represents a mechanism for maintaining a pregnancy. CD4(+)CD25(bright) regulatory T cells are known to play an important role in the development and maintenance of tolerance in peripheral tissues. However, the potential role of CD4(+)CD25(bright) T cells in maintaining human pregnancy has not been reported. In this study, we show that early human pregnancy decidua contains an abundance of CD4(+)CD25(bright) T cells, which express CD152(CTLA-4) at a high level. CD4(+)CD25(bright) T cells mediate potent inhibition of autologous T-cell proliferation by anti-CD3 stimulation. Furthermore, these cells inhibit the proliferation of autologous CD4(+)CD25(-) T cells in a dose-dependent fashion. This suppressive function of decidual CD4(+)CD25(+) T cells required cell-to-cell contact. The proportion of decidual CD4(+)CD25(bright) T cells was significantly lower in specimens from spontaneous abortion compared to those from specimens from induced abortions. These results suggest that decidual CD4(+)CD25(bright) T cells contribute to the mechanisms mediating maternal immune tolerance of conceptus antigens and therefore might contribute to the maintenance of pregnancy.
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Jung‐Hyun Park, Stanley Adoro, Terry I. Guinter et al. · Nature Immunology · 2010 · 5.8K citations · Full text
Autoimmune Disease, Lymphocyte Development, Adaptive Immune System +10
CD4+CD25high Regulatory Cells in Human Peripheral Blood
Clare Baecher‐Allan, Julia A. Brown, Gordon J. Freeman et al. · The Journal of Immunology · 2001 · 1.8K citations · Full text