title: Cell-Intrinsic gp130 Signaling on CD4+ T Cells Shapes Long-Lasting Antiviral Immunity.
abstract: The IL-6 cytokine family utilizes the common signal transduction molecule gp130, which can mediate a diverse range of outcomes. To clarify the role of gp130 signaling in vivo during acute viral infection, we infected Cd4-cre Il6st(fl/fl) mice, in which gp130 is conditionally ablated in T cells, with acute lymphocytic choriomeningitis virus. We found that by day 12, but not at day 8, after infection the number of virus-specific CD4(+) T cells was reduced in the absence of gp130, and this was sustained for up to 2 mo postinfection. Additionally, gp130-deficient T follicular helper cells had lower expression of Maf, IL-21, and ICOS, and this was accompanied by a reduction in the proportion of germinal center B cells and plasmablasts. Remarkably, at 2 mo postinfection the proportion of IgG2a/c(+) memory B cells and the systemic levels of lymphocytic choriomeningitis virus-specific IgG2 Abs were dramatically decreased, whereas there was a corresponding increase in IgG1(+) memory B cells and virus-specific IgG1 Abs. In the same animals gp130-deficient virus-specific CD8(+) T cells showed a reduced proportion of memory cells, which expressed lower levels of Tcf7, and displayed diminished recall responses on secondary infection. Mixed bone marrow chimeras revealed that the aforementioned gp130 effects on CD4(+) T cells were cell intrinsic. Overall, our data show that gp130 signaling in T cells influences the quantity and quality of long-lasting CD4(+) T cell responses as well as CD8(+) T cell- and Ab-mediated immunity after acute viral infection.
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093 j.harker@imperial.ac.uk eizuniga@ucsd.edu.
authors.forename: James A
authors.initials: JA
authors.lastname: Harker
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093.
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Wong
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Dolgoter
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jolla, CA 92093 j.harker@imperial.ac.uk eizuniga@ucsd.edu.
authors.forename: Elina I
authors.initials: EI
authors.lastname: Zuniga
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000276:immunology; D060889:Inducible T-Cell Co-Stimulator Protein / Q000096:biosynthesis; D015850:Interleukin-6 / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051257:Proto-Oncogene Proteins c-maf / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; C556694:Icos protein, mouse; D007074:Immunoglobulin G; D060889:Inducible T-Cell Co-Stimulator Protein; D015850:Interleukin-6; D007378:Interleukins; C495608:Maf protein, mouse; D051257:Proto-Oncogene Proteins c-maf; D050822:Cytokine Receptor gp130; D000098546:Interleukin-21