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

In this study interleukin (IL)-15 was examined for its ability to modulate the expression of interferon-gamma (IFN-gamma) 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 gamma(C) chain. The results demonstrate that the extent of upregulation of IFN-gamma and IL-4 mRNA was dependent on the applied cytokine (IL-2>IL-15>IL-7) and on the stimulatory signal. IFN-gamma and IL-4 mRNAs were upregulated by IL-15 in concanavalin A- (twofold) and anti-CD3 plus anri-CD28- (fivefold) stimulated T lymphocytes. IFN-gamma 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-gamma 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-gamma protein. The net effect was a dramatically increased IFN-gamma/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.