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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.<\/jats:p>","DOI":"10.4049\/jimmunol.1003166","type":"journal-article","created":{"date-parts":[[2010,12,16]],"date-time":"2010-12-16T05:31:21Z","timestamp":1292477481000},"page":"754-763","source":"Crossref","is-referenced-by-count":62,"title":["Type I IFN Substitutes for T Cell Help during Viral Infections"],"prefix":"10.1093","volume":"186","author":[{"given":"Melanie","family":"Wiesel","sequence":"first","affiliation":[{"name":"Institute for Microbiology, Swiss Federal Institute of Technology Zurich , 8093 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Kratky","sequence":"additional","affiliation":[{"name":"Institute for Microbiology, Swiss Federal Institute of Technology Zurich , 8093 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Oxenius","sequence":"additional","affiliation":[{"name":"Institute for Microbiology, Swiss Federal Institute of Technology Zurich , 8093 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,1,15]]},"reference":[{"key":"2025032410592356900_r1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/nri1413","article-title":"Helping the CD8(+) T-cell response","volume":"4","author":"Bevan","year":"2004","journal-title":"Nat. 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