title: Type I IFN substitutes for T cell help during viral infections.
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.
authors.affiliation: Institute for Microbiology, Swiss Federal Institute of Technology Zurich, 8093 Zurich, Switzerland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Wiesel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kratky
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D024201:Bystander Effect / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D007370:Interferon Type I / Q000096:biosynthesis / Q000502:physiology*; D019409:Interleukin-15 / Q000096:biosynthesis / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D014615:Vaccinia / Q000276:immunology / Q000473:pathology / Q000821:virology; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D019409:Interleukin-15; D007376:Interleukin-2