Gamma/delta T cells in placenta and skin: their different functions may support the paradigm of microchimerism in systemic sclerosis.

Increased amounts of foetal cells persisting after pregnancy could be involved in the pathagetiesis of systemic sclerosis (SSc) and other autoimmune diseases. Evidence suggests a specific role for a subset of T lymphocytes showing the γ/δ T cell receptor (TCR) at the foetal/maternal interface, γ/δ T cells significantly increase in the early pregnancy decidua and recognize trophoblast antigens, probably a highly evolutionarily conserved molecule such as Hsp60 or Hsp60-derived peptides, and are likely to suppress the maternal anti-foetal immune response via TGFβ production, thus contributing to pregnancy maintenance. The similarity between the presence of host γ/δ T cells in pregnancy decidua and in SSc skin Suggests that the functional activities of these cells can be differentially modulated by several mechanisms including the nature of the antigen and the involved organs. To support pregnancy, the decidual microenvironment might induce a Th2 activity of host Vδ1+ T cells. On the contrary, either the presence of foetal cells in the skin of SSc patients or an as yet unidentified stimulus (i.e. infections), may trigger Vδ1+ T cells toward the ThI phenotype with the subsequent activation of cytotoxicity and modulation of the cytotoxic α/β acquired T cell response. On these grounds, understanding the mechanisms which prevent the maternal immune system from rejecting a semiallogenic foetus could be helpful to understand the development of some autoimmune diseases, and potentially to develop new targeted therapeutic strategies.