Murine Female Reproductive Tract Intraepithelial Lymphocytes Display Selection Characteristics Distinct from Both Peripheral and Other Mucosal T Cells

Despite immense effort, the development of vaccines effective at mucosal sites has proceeded at a faltering pace. Efforts concentrating on humoral immunity but neglecting cellular immunity may be misdirected by ignoring many viral mucosal pathogens. Improved understanding of the development and maintenance of lymphocytes populating the reproductive tract (rtIELs) may inform advances in vaccination strategies for sexually transmitted diseases. Recent studies highlight tissue-specific differences in the development of mucosal immunity and suggest that the local milieu may play a role in selection, maintenance and function of resident lymphocytes. Here, we describe MHC class I and thymus dependence of subpopulations of rtIELs. TCRalphabeta+ CD8alphabeta+ T cells in the periphery, intestine, and female reproductive tract are all developmentally dependent on classical class I MHC and the thymus. TCRalphabeta+ CD8alphaalpha+ are absent from the periphery and the rtIELs, but are present and classical MHC class I-independent, in the intestine. In contrast to intestinal TCRgammadelta+ cells, TCRgammadelta+ rtIELs are CD8 negative and thymus dependent. In contrast to peripheral TCRgammadelta+ cells, murine TCRgammadelta+ rtIELs express not a diverse array of Vdelta genes, but rather, a canonical Vdelta1. In summary, lymphocytes isolated from the murine female reproductive tract have characteristics distinct from both peripheral T cells and those found at other mucosal sites. Therefore, for the purpose of vaccination strategies, the female reproductive tract should be regarded neither as peripheral nor mucosal, but rather as a tissue with distinctive immunological characteristics.