Abstract
Interleukin-2 (IL-2) plays a central role in the differentiation of functionally competent CD8+ memory T cells. In this study, we found that in the absence of IL-2 signals, the differentiation of short-lived CD8+ effector T cells and tissue-residing effector memory CD8+ T cells in response to acute infection was greatly impaired. Due to their shared signaling apparatus, we explored the hypothesis that IL-15 signals might also contribute to the differentiation and survival of these populations. In line with this hypothesis, we observed an additional impairment in the differentiation and persistence of short-lived effector/effector memory cells in the spleen when both IL-2 and IL-15 signals were absent. Furthermore, in the absence of IL-2 and IL-15 signals this population disappeared completely by day 15. In contrast, joint inhibition of IL-2 and IL-15 signals had no further impact on the differentiation of tissue-residing CD8+ effector memory T cells. While IL-2 and IL-15 contributed to the differentiation of short-lived effector cells during the primary response, IL-15 continued to play a mandatory role in the survival of these cells during contraction and memory. These findings delineate a joint role for IL-15 and IL-2 in the differentiation of short-lived CD8+ effector cells but point to unique roles for IL-15 and IL-2 in promoting the survival of short-lived effector/effector memory cells in the spleen and the differentiation of tissue-residing effector memory cells, respectively.