The case for extrathymic development of vaginal T lymphocytes

The vaginal tract mucosa is populated by a small, yet phenotypically diverse and functionally significant, subset of T cells that plays a major role in local cell-mediated immunity. Although phenotypic and functional characteristics of vaginal T cells have received some attention in recent years, little is known about the development of this cell population. In this mini review, the developmental origins of vaginal T cells are traced from published work related to vaginal T cells, the vaginal mucosa environment and vaginal tract infection animal models. A CD3+TCR+CD2+CD5+B220− (CD3+B220−) subpopulation, which is mostly CD4+, makes up 30–40% of vaginal T lymphocytes. This population consists of a TCRαβ+ subset and TCRγδ+ subset. While CD3+B220−TCRαβ+ vaginal T cells exhibit phenotypic and functional properties consistent with that of peripheral T cells, CD3+B220−TCRγδ+ vaginal T cells exhibit unique phenotypic and functional features that set them apart from other TCRγδ+ T cell subsets populating the periphery or other mucosal areas. The vaginal mucosa is populated also by CD3+TCRαβ+CD4−/8−B220+CD2−CD5− T cells (CD3+B220+) whose relative predominance increases significantly in systemic T cell deficiency. This subset is generally unresponsive to TCR-mediated stimuli and expresses high levels of CD25, perhaps indicative of a regulatory role. Current data suggest that, while CD3+B220− vaginal T cells are mostly thymic in origin, CD3+TCRαβ+B220+ cells are exclusively extrathymic.