Interferon Gamma Enhances Clonal Expansion and Survival of CD4 + T Cells

Abstract

Interferon-γ (IFN-γ) serves numerous functions in the regulation of the immune response. During the early phase of the immune response IFN-γ is produced by natural killer and natural killer T cells. Although the effects of this cytokine on antigen presenting cells and other cell types are known, its direct role on CD4⁺ T cells remains unclear. We demonstrate that CD4⁺ T cells exposed to IFN-γ proliferate more vigorously than the controls in response to signals through the antigen receptor. The increased proliferation of IFN-γ-treated CD4⁺ T cells is not due to enhanced signaling through the antigen receptor, but is accounted for by their increased survival. Our data suggest that enhanced survival of IFN-γ-treated CD4⁺T cells is independent of signal transducer and activator of transcription 1 (STAT 1), a transcription factor that controls the expression of a variety of IFN-γ-targeted genes. In addition, we demonstrate that independent of STAT1, IFN-γ treatment increases the expression of double-stranded RNA-dependent protein kinase, a kinase involved in regulating protein synthesis. Taken together, our findings suggest a direct role of IFN-γ on unstimulated CD4⁺ T cells that is likely to enhance the advent of adaptive immunity by augmenting their survival during the initiation of the immune response.