title: Type I IFN-dependent T cell activation is mediated by IFN-dependent dendritic cell OX40 ligand expression and is independent of T cell IFNR expression.
abstract: Type I IFNs are important for direct control of viral infection and generation of adaptive immune responses. Recently, direct stimulation of CD4(+) T cells via type I IFNR has been shown to be necessary for the formation of functional CD4(+) T cell responses. In contrast, we find that CD4(+) T cells do not require intrinsic type I IFN signals in response to combined TLR/anti-CD40 vaccination. Rather, the CD4 response is dependent on the expression of type I IFNR (IFNαR) on innate cells. Further, we find that dendritic cell (DC) expression of the TNF superfamily member OX40 ligand was dependent on type I IFN signaling in the DC, resulting in a reduced CD4(+) T cell response that could be substantially rescued by an agonistic Ab to the receptor OX40. Taken together, we show that the IFNαR dependence of the CD4(+) T cell response is accounted for exclusively by defects in DC activation.
authors.affiliation: Integrated Department of Immunology, University of Colorado Denver and National Jewish Health, Denver, CO 80206, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Kurche
authors.forename: Catherine
authors.initials: C
authors.lastname: Haluszczak
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: McWilliams
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Sanchez
authors.forename: Ross M
authors.initials: RM
authors.lastname: Kedl
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D007370:Interferon Type I / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053278:OX40 Ligand; D011828:Radiation Chimera / Q000276:immunology; D053633:Receptor, Interferon alpha-beta / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors; D053633:Receptor, Interferon alpha-beta