Cell-intrinsic IL-27 and gp130 cytokine receptor signaling regulates virus-specific CD4? T cell responses and viral control during chronic infection.

ABSTRACT: The outcome of chronic viral infections, which affect millions of people worldwide, is greatly dependent on CD4? T cells. Here we showed that T cell-specific ablation of the common interleukin-6 (IL-6) family receptor, gp130, profoundly compromised virus-specific CD4? T cell survival, T follicular helper responses, and IL-21 production at late stages of chronic lymphocytic choriomeningitis virus (LCMV) infection. These effects were cell intrinsic for CD4? T cells and were accompanied by a reduction of CD8? T cells, antibodies, and a severe failure in viral control. We identified IL-27 as a gp130 cytokine that promoted antiviral CD4? T cell accumulation in vivo and that rapidly induced IL-21 ex vivo. Furthermore, IL-27R was critical for control of persistent LCMV in vivo. These results reveal that gp130 cytokines (particularly IL-27) are key regulators of CD4? T cell responses during an established chronic viral infection, empowering both humoral and cytotoxic immunity.

SUBMITTER: Harker JA 

PROVIDER: S-EPMC4701058 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature