Lack of IL-7 and IL-15 signaling affects interferon-γ production by, more than survival of, small intestinal intraepithelial memory CD8+ T cells

Survival of antigen-specific CD8+ T cells in peripheral lymphoid organs during viral infection is known to be dependent predominantly on IL-7 and IL-15. However, little is known about a possible influence of tissue environmental factors on this process. To address this question, we studied survival of memory antigen-specific CD8+ T cells in the small intestine. Here, we show that 2 months after vaccinia virus infection, B8R20–27/H2-Kb tetramer+ CD8+ T cells in the small intestinal intraepithelial (SI-IEL) layer are found in mice deficient in IL-15 expression. Moreover, SI-IEL and lamina propria lymphocytes do not express the receptor for IL-7 (IL-7Rα/CD127). In addition, after in vitro stimulation with B8R20–27 peptide, SI-IEL cells do not produce high amounts of IFN-γ neither at 5 days nor at 2 months postinfection (p.i.). Importantly, the lack of IL-15 was found to shape the functional activity of antigen-specific CD8+ T cells, by narrowing the CTL avidity repertoire. Taken together, these results reveal that survival factors, as well as the functional activity, of antigen-specific CD8+ T cells in the SI-IEL compartments may markedly differ from their counterparts in peripheral lymphoid tissues.