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

Abstract

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.

Identification of enhanced IFN-γ signaling in polyarticular juvenile idiopathic arthritis with mass cytometry

“…There is evidence in murine studies that IFN-γ can enhance the proliferation and survival of CD4 T cells (42,43). Interestingly, Ki-67 expression was higher in both stratifying and nonstratifying subsets of CD4 T cells and classical monocytes.…”

Immunotoxicological effects of streptozotocin and alloxan: In vitro and in vivo studies

“…Furthermore, IFN-␥, but not IL-2 production after Con-A stimulation for 5 days was higher in cells from STZ-injected mice than in cells from mice injected with ALX. Since it has been demonstrated that INF-␥ enhances the expansion and survival of CD4 + cells [21] the increase in cell proliferation of STZ-splenic cells might be due to enhanced production of INF-␥ after allogeneic stimulation. In addition, the high IFN-␥ production in Con-A-activated STZ splenocytes suggests that STZ treatment may affect the immune system in different way compared to that seen after ALX treatment.…”

Responses of the spleen to intraamniotic lipopolysaccharide exposure in fetal sheep

“…Both Th1 and Th2 cytokines were elevated at 24 h after LPS administration with upregulation of IFNγ as the prominent Th1 cytokine and increased levels of IL4 and IL5 as Th2 cytokines. As these cytokines stimulate the differentiation of T helper and effector cells, the early increase in CD3 expression in the spleen might be under the influence of these cytokine changes (26).…”