T cell immunity and the etiology and pathogenesis of preeclampsia.

Preeclampsia is more common in nulliparous women, their first pregnancies with a new partner in multiparous women, pregnant women with short duration of cohabitation, and in pregnancies with donor eggs, where the fetus is completely foreign to the mother. The epidemiological study findings strongly suggest that inadequate induction of tolerance to paternal/fetal antigens is involved in the pathogenesis of preeclampsia. This review proposes that preeclampsia may be caused by a reduction in paternal/fetal antigen-specific regulatory T (Treg) cells and decreased PD-1 expression on clonally expanded CD8 effector memory T (T) cells, resulting in a breakdown of mother-to-fetus tolerance. The immune environment of preeclampsia is clearly different from that of recurrent pregnancy loss (RPL). In preeclampsia, cloned Treg cells decreases, and PD-1 expression on cloned CD8T decreased. In RPL, the total number of Treg cells decreased, and the total number of clonally expanded CD8T cells increases. In addition to these changes, increased differentiation of Th17 cells has also been observed in preeclampsia. This change is caused by soluble endoglin, that is increased in preeclampsia, neutralizing TGFβ. These immunological changes make the fetus more susceptible to attacks from maternal T cells.