title: Unique features of naive CD8+ T cell activation by IL-2.
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-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.
authors.affiliation: Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia;
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Cho
authors.forename: Hee-Ok
authors.initials: HO
authors.lastname: Kim
authors.forename: Kyu-Sik
authors.initials: KS
authors.lastname: Kim
authors.forename: Deok-Hwan
authors.initials: DH
authors.lastname: Yang
authors.forename: Charles D
authors.initials: CD
authors.lastname: Surh
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sprent
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D007376:Interleukin-2 / Q000276:immunology*; D053616:Janus Kinase 3 / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology*; D058408:Th1-Th2 Balance
chemical_list: D016207:Cytokines; C491198:Eomes protein, mouse; D007376:Interleukin-2; D020825:T-Box Domain Proteins; D019869:Phosphatidylinositol 3-Kinases; D053616:Janus Kinase 3; D051058:Oncogene Protein v-akt