JOURNAL OF IMMUNOLOGY, v.191, no.11, pp.5559 - 5573
Publisher
AMER ASSOC IMMUNOLOGISTS
Abstract
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-kB, 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. The Journal of Immunology, 2013, 191: 5559–5573.