Human Pregnancy Levels Of Estrogen And Progesterone Contribute To Humoral Immunity By Activating T-Fh/B Cell Axis

Circulating T-FH(cT(FH)) cells express CXCR5, PD-1, and, when activated, ICOS, and release IL-21. According to the production of IFN-gamma, IL-4, and IL-17 and expression of FoxP3, these cells are also classified as cT(FH)1, cT(FH)2, cT(FH)17, and cT(FR)cells, respectively. This CD4(+)T-cell subset is pivotal to efficient humoral immunity, and pregnancy appears to favor IgG production. Here, not only pregnancy amplified the in vivo production of anti-HBsAg IgG in HBV immunized women, but the frequency of cT(FH)cells was directly correlated with estradiol levels. In vitro, pregnancy-related dose of 17-beta-estradiol (E2) directly increased the percentage of different cT(FH)subsets. While E2 and progesterone (P4) increased the proportion of differentiated T(FH)cells derived from naive CD4(+)T-cells, only E2 amplified the release of IL-21 in those cell cultures. In addition, E2 and P4 increased the proportion of memory B cells and plasma cells, respectively. In SEB-activated B/T(FH)cell co-cultures, E2, in the presence of P4, increased the production of total IgG. Finally, among the hormones, P4 was stronger in upregulating the percentage of IL-10(+)T(FR)cells. Collectively, our findings suggested that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cT(FH)and B cell subsets.