title: IFN-λ exerts opposing effects on T cell responses depending on the chronicity of the virus infection.
abstract: IFN-λ induces an antiviral state in many cell types and may contribute to the overall inflammatory environment after infection. Either of these effects may influence adaptive immune responses, but the role of type 3 IFNs in the development of primary and memory T cell responses to infection has not been evaluated. In this study, we examined T cell responses to acute or persistent lymphocytic choriomeningitis virus infection in IFN-λR1-deficient mice. Following acute infection, we find that IFN-λR1-deficient mice produced normal levels of IFN, robust NK cell responses, but greater than normal CD4+ and CD8+ T cell responses compared with wild type BALB/c mice. There were more T cells that were IL-7R(hi) and, correspondingly, the IFN-λR-deficient mice showed a 2- to 3-fold increase in memory T cell number. The inhibitory effect of IFN-λR expression was independent of direct cytokine signaling into T cells. In contrast with acute infection, the IFN-λR-deficient mice generated markedly diminished T cell responses and had greater weight loss compared with wild type mice when confronted with a highly disseminating variant of lymphocytic choriomeningitis virus. These data indicate that IFN-λR limits T cell responses and memory after transient infection but augments T cell responses during persisting infection. Thus, the immune-regulatory functions for IFN-λR are complex and vary with the overall inflammatory environment.
authors.affiliation: Department of Genetics, University of North Carolina School of Medicine, Chapel Hill, NC 27599.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Misumi
authors.forename: Jason K
authors.initials: JK
authors.lastname: Whitmire
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D056724:Immunity, Humoral; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
chemical_list: D017471:Receptors, Interferon; D007371:Interferon-gamma