Fetus specific T cell modulation during fertilization, implantation and pregnancy

Recently there is an increasing interest in aspects of a more specific immunoregulation during pregnancy. Understanding these mechanism might have a broader application not only for reproductive immunology but also in general for biology and medicine. Especially the induction, already before conception, of feto-specific T cells with a possibly regulatory function gives a biological explanation of local immunotolerance at the maternal fetal interface, supporting the epidemiological evidence of a feto/paternal-specific immuneregulation. Understanding the expression of specific HLA-classes on trophoblast and the crosstalk of these antigens with various cell types, specifically modulated in the decidua, resulting in the secretion of cytokines and (angiogenic) chemokines has given us a more and more detailed understanding of this regulation. This regulation could be induced by fetal cells circulating in the mother (microchimerism) and from the interaction with fetal subcellular fractions as exosomes, but also from paternal antigens present in seminal fluid. Molecular interaction between paternal and fetal antigens and receptors in endometrium and the decidua are discussed. This review highlights besides uNK cells, especially the function of CD4+ and CD8+ T cells with a regulatory function in the context of recurrent miscarriage and pre-eclampsia. Besides HLA, also male-specific minor histocompatibility antigens and the genetic background for these pregnancy complications are discussed.