Regulatory T cells mediate maternal tolerance to the fetus

Nature Immunology 5, 266 - 271 (2004)

Speaker : 盧 淑 君                     Time : 13:00-14:00, Apr. 28, 2004

Commentator: 楊 倍 昌 教授           Place : Room 601

Abstract:

How does the maternal immune system tolerate the persistence of paternal alloantigens during pregnancy? Several localized mechanisms have previously been described that contribute to fetal evasion from immune attack¹. Nevertheless, maternal alloreactive lymphocytes can still be detected. The number of naturally occurring regulatory T cells (CD4⁺ CD25⁺)² in the lymph nodes and spleen of pregnant mice was markedly increased compared with non-pregnant control mice. This expansion of the CD4+CD25+ T cell population even occurred when mice were mated with syngeneic males, indicating that the presence of fetal alloantigen is not required to drive expansion of the CD4⁺ CD25⁺ T-cell pool. In vitro, these cells could suppress the proliferation of alloreactive cells in a mixed lymphocyte reaction. Furthermore, when whole lymphocyte preparations or CD25⁺ cell depleted preparations from pregnant mice were adoptively transferred to nude female mice that were subsequently mated, those that received samples depleted of CD25⁺ cells did not sustain normal pregnancy. However, if the mice that received CD25+ cell-depleted preparations were mated with a syngeneic male, pregnancy was normal, indicating that the regulatory function of these T cells is only required when the fetus expresses alloantigen, which is inevitable under non-experimental circumstances. The presence of these regulatory populations might explain the observed remission of some autoimmune diseases and enhanced maternal tolerance to some paternal grafts during pregnancy. Future experiments hope to determine whether these cells are important in preventing pregnancy failures in humans.

References :

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2.     Sakaguchi, S. et al. Immunologic tolerance maintained by CD25⁺CD4⁺ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol. Rev. 182, 18–32 (2001).