Interferon gamma enhances clonal expansion and survival of CD4+ T cells.
Interferon-gamma (IFN-gamma) serves numerous functions in the regulation of the immune response. During the early phase of the immune response IFN-gamma 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-gamma proliferate more vigorously than the controls in response to signals through the antigen receptor. The increased proliferation of IFN-gamma-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-gamma-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-gamma-targeted genes. In addition, we demonstrate that independent of STAT 1, IFN-gamma 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-gamma 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.
Reed
Jennifer M
JM
Department of Biology, Villanova University, Villanova, Pennsylvania 19085, USA.
Branigan
Patrick J
PJ
Bamezai
Anil
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002470:Cell Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism
D011948:Receptors, Antigen, T-Cell; D050794:STAT1 Transcription Factor; D007371:Interferon-gamma; D019892:eIF-2 Kinase; D048049:Extracellular Signal-Regulated MAP Kinases