Pregnancy favors the expansion of circulating functional follicular helper T Cells

Pregnancy favors antibody production, and some evidence has suggested a direct effect of estrogen on B cells. The impact of pregnancy on circulating follicular helper T (TFH) cells, typically identified by the expression of CD45RO and CXCR5, has not been previously investigated. Here, the percentage of TFH cells, co-expressing or not PD-1, ICOS, or CXCR3 markers was significantly higher in pregnant women (PW) as compared with non-pregnant ones (nPW). Furthermore, the percentage of CXCR3+ TFH cells able to produce IL-6, IL-21, and IL-10 was significantly higher in PW than nPW. Interestingly, anti-CMV and anti-HBs antibody titers were significantly higher in the plasma of PW and were directly correlated with IL-21-producing CXCR3+ TFH cells. Finally, peripheral estrogen levels, but not progesterone, were positively related to either PD-1+ CXCR3+ TFH cells or plasma anti-CMV and anti-HBs IgG antibodies. In summary, our data suggests a positive effect of pregnancy on the proportion of CD4+ T cell subset specialized in helping B cells. This phenomenon, which could be related to the high estrogen levels produced during pregnancy, may help to explain why pregnancy favor humoral immunity.