Correlations of the expression of γδ T cells and their co‐stimulatory molecules TIGIT,PD‐1, ICOS and BTLA with PR and PIBF in the peripheral blood and decidual tissues of women with unexplained recurrent spontaneous abortion

Semi‐allogeneic embryos are not rejected by the maternal immune system due to maternal–fetal immune tolerance. Progesterone (P) receptor (PR)‐expressing γδ T cells are present in healthy pregnant women. In the presence of P, these cells secrete an immunomodulatory protein called progesterone‐induced blocking factor (PIBF), which can facilitate immune escape and is important in preventing embryonic rejection. This work investigated the correlations of the expression of γδ T cells and their co‐stimulatory molecules T cell immunoglobulin and ITIM domain (TIGIT), programmed cell death 1 (PD‐1), inducible co‐stimulator (ICOS) and B and T lymphocyte attenuator (BTLA) with progesterone receptor (PR) and progesterone‐induced blocking factor (PIBF) in peripheral blood and decidual tissue in women with unexplained recurrent spontaneous abortion (URSA) and normal pregnant (NP) women. We confirmed that γδ T cell proportions and PIBF expression in the peripheral blood and decidua of URSA women decreased significantly, while PR expression in decidua decreased. However, TIGIT, PD‐1, ICOS and BTLA expression in γδ T cells in peripheral blood did not change, while TIGIT and PD‐1 expression in γδ T cells in decidua increased significantly. Under the action of PHA‐P (10 µg/ml), co‐blocking of TIGIT (15 µg/ml) and PD‐1 (10 µg/ml) antibodies further induced γδ T cell proliferation, but PIBF levels in the culture medium supernatant did not change. At 10^?10 M P, γδ T cells proliferated significantly, and PIBF concentrations in the culture medium supernatant increased. γδ T cells co‐cultured with P, TIGIT and PD‐1 blocking antibodies showed the most significant proliferation, and PIBF concentrations in the culture medium supernatant were the highest. These results confirm that P is necessary for PIBF production. The TIGIT and PD‐1 pathways participate in γδ T cell proliferation and activation and PIBF expression and play important roles in maintaining pregnancy.