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  • Title: Type I IFN substitutes for T cell help during viral infections.
    Author: Wiesel M, Kratky W, Oxenius A.
    Journal: J Immunol; 2011 Jan 15; 186(2):754-63. PubMed ID: 21160039.
    Abstract:
    Certain virus infections depend on the presence of T cell help for the generation of primary CD8(+) T cell responses. However, the mechanisms that render these particular viral infections T cell help dependent is largely unknown. In this study, we compared CD8(+) T cell responses elicited by lymphocytic choriomeningitis virus infection, as prototype of a T cell help independent infection, with T cell help dependent CD8(+) T cell responses induced by vaccinia virus infection. In this paper, we show that a key parameter decisive for T cell help independence is the ability of an infectious agent to stimulate early and robust production of type I IFN. Experimental provision of type I IFN during VV infection rendered the ensuing CD8(+) T cell response completely T cell help independent. Our results support a model in which type I IFN has to be present during the first 3 d of Ag encounter and has to act directly on the responding CD8(+) T cells to promote their survival and effector differentiation. We show that type I IFN signaling on responding CD8(+) T cells induces profound upregulation of CD25 and increased IL-2 expression; however, neither this nor IL-15 accounts for the type I IFN effects on responding CD8(+) T cells. Thus, type I IFN can effectively replace the requirement of T cell help by directly promoting CD8(+) T cell survival and differentiation independent of the type I IFN-induced cytokines IL-2 and IL-15.
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