Unique Features of Naive CD8+ T Cell Activation by IL-2

IL-2 has a pervasive influence on the immune system and dictates the survival and differentiation of multiple T cell subsets, including CD4 regulatory T cells, CD4 Th cells, and CD8 memory cells. IL-2 is synthesized by T cells during the early stages of the immune response and promotes T cell expansion and effector cell generation after initial activation via TCR signaling. Based on studies with activated T cell lines maintained in vitro, IL-2 is known to activate multiple signaling pathways that show considerable overlap with the pathways elicited via the TCR. In this paper, we have examined IL-2 signaling under TCR-independent conditions, namely by culturing purified resting naive CD8 T cells with IL-2 in the absence of Ag or APC. Under these conditions, we show in this study that IL-2 elicits a unique pattern of signaling associated with strong lymphocyte-specific protein tyrosine kinase/JAK3-dependent activation of the PI3K/AKT pathway with little or no involvement of STAT5, NF-κB, or the calcineurin/NFAT pathways. Such signaling induces marked proliferation associated with rapid and selective expression of eomesodermin but not T-bet and differentiation into long-lived central memory cells after adoptive transfer.