Cell-Intrinsic gp130 Signaling on CD4+ T Cells Shapes Long-Lasting Antiviral Immunity

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.