IL-15 promotes survival but not effector function differentiation of CD8(+) TCR alpha beta(+) intestinal intraepithelial lymphocytes

CD8 single-positive cells, including CD8 alpha alpha(+) and CD8 alpha beta( +) subsets, constitute the majority of TCR alpha beta(+) intestinal intraep ithelial lymphocytes (alpha beta iIEL) in mice. CD8(+) alpha beta iIEL show significantly weaker responses to TCR stimulation in the presence of exoge nous IL-2 than do CD8(+) T cells of the central immune system, IL-15 is a T cell growth factor likely expressed in the intestine mucosa, To understand the role of IL-15 in CD8(+) alpha beta iIEL biology, we compared the effec ts of exogenous IL-15 and IL-2 on the survival and primary responses of the two CD8+ alpha beta iIEL subsets in vitro. In contrast to the death of sim ilar to 60% of both CD8 alpha alpha(+) and CD8 alpha beta(+) iIEL cultured in IL-2 with or without TCR stimulation, IL-15 promoted survival of the CD8 alpha alpha(+) subset in the presence of TCR stimulation and promoted surv ival of both subsets in the absence of TCR stimulation. The higher prolifer ation level of TCR stimulated CD8 alpha alpha(+) ap iIEL cultured in IL-15 compared with those cultured in IL-2 is likely due to IL-15's prosurvival e ffects. In addition, unlike exogenous IL-2, exogenous IL-15 did not support the effector functions of either iIEL subsets, including IFN-gamma product ion, IL-4-induced Th2 cytokine product:ion, and anti-TCR mAb redirected cyt otoxicity. These findings demonstrate that IL-15 and IL-2 are functionally distinct and suggest that IL-15 plays a unique role in the maintenance of t he CD8+ ap iIEL pool in the absence of Ag stimulation and in the survival a nd expansion of CD8 alpha alpha(+) alpha beta iIEL upon Ag stimulation.