Interleukin‐15 differentially enhances the expression of interferon‐γ and interleukin‐4 in activated human (CD4+) T lymphocytes

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Abstract
In this study interleukin (IL)‐15 was examined for its ability to modulate the expression of interferon‐γ (IFN‐γ) and IL‐4 in activated human T lymphocytes. The effect of IL‐15 was compared with IL‐2 and IL‐7, cytokines all known to use the IL‐2 receptor γC chain. The results demonstrate that the extent of upregulation of IFN‐γ and IL‐4 mRNA was dependent on the applied cytokine (IL‐2>IL‐15>IL‐7) and on the stimulatory signal. IFN‐γ and IL‐4 mRNAs were upregulated by IL‐15 in concanavalin A‐ (twofold) and anti‐CD3 plus anti‐CD28‐ (fivefold) stimulated T lymphocytes. IFN‐γ mRNA accumulation, but not IL‐4 mRNA, was additively upregulated by IL‐15 plus IL‐7 (ninefold) in anti‐CD3 stimulated T lymphocytes, and bypassed the requirement of CD28 signalling. Fluorescence‐activated cell sorting (FACS) experiments demonstrated that IFN‐γ mRNA was upregulated by IL‐15 in both CD4+ and CD8+ T lymphocytes, whereas IL‐4 mRNA accumulation predominantly occurred in CD4+ cells. Preincubation of highly purified CD4+ T lymphocytes during 7 days with IL‐15 and/or IL‐7, followed by activation, also showed enhanced IL‐4 protein secretion, but predominantly upregulated IFN‐γ protein. The net effect was a dramatically increased IFN‐γ/IL‐4 ratio. Taken together, IL‐15 and IL‐7 can act as costimulatory signals, which may favour a T helper 1 (Th1) immune response, particularly in the absence of sufficient CD28 costimulation.