Distinct PLZF+ T cells characterize fetal mucosal adaptive immunity.

The human fetal immune system is comprised of unique, functional T cell populations. The fetal thymus is uniquely enriched for a number of non-conventional T cells that acquire functional properties during development in the thymus, and include PLZF+ CD4+ T cells. Fetal PLZF+ T cells are thought to play a role in protective immunity, which led us examine their presence in the fetal intestine. We found that PLZF+ T cells accumulate in the lamina propria of the fetal intestine compared to the mesenteric lymph nodes, spleen, and thymus. Further characterization revealed the majority of intestinal PLZF+ CD4+ T cells co-express the C-type lectin receptor CD161, have an effector memory-like phenotype, and possess strong inflammatory potential. The transcription factor PLZF is associated with iNKT and MAIT cells in both human and mouse, and both of these populations are present in the human fetal intestine, albeit in small proportions. Our goal is to provide a thorough characterization of fetal PLZF+ T cells and determine whether they constitute a novel T cell population. To achieve this, we will complement our phenotypic and functional data with RNA-sequencing to determine whether PLZF+ CD4+ T cells possess a distinct transcriptome from other mucosal T cell populations.