The regulation of T-cell cytokine production by ICOS-B7H2 interactions at the human fetomaternal interface.

Although T cells are the most common decidual lymphocyte subset in late pregnancy, little is known about the mechanisms controlling their function. Costimulatory signaling, mediated by inducible costimulator (ICOS)-B7H2 interactions, is a known potent regulator of T-cell activation. We aimed to determine its role in fetomaternal immunity. T cells from matched peripheral blood and term decidua were assessed for ICOS, CD4/CD8, CD45RA/CD45RO and Foxp3 expression and for alterations in cytokine production upon ICOS-B7H2 ligation. We also assessed ICOS-B7H2 communication between T cells and a trophoblast cell line (JEG3). Strong ICOS expression was observed on CD4 and CD8 decidual (d)T cells, but not peripheral (p)T cells. Among dT cells, ICOS expression was higher on the predominant CD45RO(+) cell population compared with CD45RA(+) cells. Strong ICOS expression was also seen on CD4(+)Foxp3(+) regulatory T cells in the decidua. ICOS ligation enhanced T-cell secretion of interferon-gamma (IFN-γ) and interleukin-10 (IL-10), but not IL-2. The impact of ICOS stimulation was more remarkable in dT cells when compared with pT cells. T cells co-cultured with JEG3 cells promoted T-cell production of IFN-γ and IL-10, an effect blocked by antibody-specific masking of major histocompatibility class I or B7H2. These findings suggest that T-cell cytokine modulation by ICOS-B7H2 interactions is important in the delicate immune balance at the fetomaternal interface.