Materno-fetal immunobiology in normal pregnancy and its possible failure in recurrent spontaneous abortion?

Abstract

Many features contributing to the success of pregnancy in humans have been identified over the last 20 years. Trophoblast cells (which form the interface of fetal tissue with the mother) have specialized immunological features which may confer unique transplantation protection for the fetus throughout pregnancy. Both syncytiotrophoblast and cytotrophoblast cells do not express classical class I [human leucocyte antigen (HLA)-A or -B] or II (HLA-DP, -DQ or -DR) major histocompatibility complex (MHC) alloantigens, and the regulation of these cell surface glycoproteins appears to be at the transcriptional level. In contrast, extravillous cytotrophoblast cells express the non-classical class I MHC molecule HLA-G. One form of HLA-G (HLA-G1) is potentially capable of presenting a variety of peptide antigens to T cells. Alternatively, HLA-G may act as a cell surface class I MHC molecule, protecting cytotrophoblast from maternal MHC non-restricted natural killer (NK) cell attack; the expression of HLA-G by otherwise HLA-null cell transfectants has been shown to decrease their sensitivity to NK cell-mediated cytolysis. All fetal trophoblast populations throughout gestation express high levels of cell surface complement regulatory proteins, providing protection from complement-mediated damage at the materno-fetal interface. Analyses of trials with allogeneic leucocytes for the treatment of recurrent spontaneous abortion show little evidence of an improved success rate in immunized patients.