Uterine CD11c+ cells induce the development of paternal antigen-specific Tregs via seminal plasma priming. (September 2020) - Shima, Tomoko
Highlights: MHC class II and CD86 on uterine DCs in allogeneic pregnancy were decreased. Uterine DCs in allogeneic pregnancy induced paternal antigen-specific Tregs. Seminal fluid priming is important for the induction of tolerogenic DC. Abstract: Tolerogenic dendritic cells (tDCs) play a central role in the development of paternal antigen-specific regulatory T cells (Tregs) during pregnancy. We examined whether uterine CD11c + antigen presenting cells (APC) induced paternal antigen-specific tolerance in allogeneic pregnant mice. Female BALB/c mice were mated with male DBA/2 mice, and their surface markers of APCs were studied using flow cytometry. After allogeneic mating, the uterine APCs exhibited significantly decreased expression of major histocompatibility complex (MHC) class II on day 3.5 post-coitus (pc) and day 5.5 pc. To analyze how seminal fluid affects surface markers of APCs, female BALB/c mice were mated with male mice that had undergone seminal vesicle excision (SVX). No reductions of MHC class II expression on APCs were seen in these mice. To analyze APC functions, a mixed lymphoid reaction (MLR) assay to paternal splenocytes was performed. Uterine APCs from allogeneic pregnant mice significantly suppressed the MLR reaction, but APCs from SVX mated mice did not suppress the MLR reaction Uterine APCs induced paternal antigen (Mls1a)-specific Treg development in vitro, but not in mice that mated with allogeneic SVX mice. These findings suggest that seminal fluid priming expands the paternal antigen-specific Treg population by inducing APCs development.