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 TCRalphabeta(+) subset and TCRgammadelta(+) subset. While CD3(+)B220(-)TCRalphabeta(+) vaginal T cells exhibit phenotypic and functional properties consistent with that of peripheral T cells, CD3(+)B220(-)TCRgammadelta(+) vaginal T cells exhibit unique phenotypic and functional features that set them apart from other TCRgammadelta(+) T cell subsets populating the periphery or other mucosal areas. The vaginal mucosa is populated also by CD3(+)TCRalphabeta(+)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(+)TCRalphabeta(+)B220(+) cells are exclusively extrathymic.