CONTRIBUTION OF P56(LCK) TO THE UP-REGULATION OF CYTOKINE PRODUCTION AND T-CELL PROLIFERATION BY IL-2 IN HUMAN CD3-STIMULATED T-CELL CLONES

Interaction of the interleukin 2 receptor (IL-2R) beta chain with the lymphocyte-specific protein tyrosine kinase (PTK), p56(lck), has led t o the speculation that p56(lck) participates in growth signal transduc tion. Although activation of T cells with interleukin 2 (IL-2) results in the activation of p56(lck), accumulating data support the notion t hat Lck does not play an essential role in mitogenic signal delivery f rom the IL-2R. Since this src-related PTK has been shown to enhance TC R/CD3-mediated T cell responsiveness, here we investigated whether act ivation of Lck by IL-2 could contribute to enhance TCR/CD3-mediated T cell functions. This was achieved by using human CD4(+)-cloned T cells and comparing the effects of IL-2 on p56(lck) kinase activation and c ytokine production. Results show that p56(lck) kinase nase activity in creased as early as 1 min, reached a maximum within 5 min and decrease d within 60 min after IL-2 stimulation. Such treatment with IL-2 also resulted in enhancing T cell responsiveness to CD3+PMA stimulation, as assessed by IL-2 and IFN-gamma secretion and by T cell proliferation. This increase of T cell functions was correlated with IL-2-induced p5 6(lck) activation in both dose-response and time-course experiments. T aken together these results strongly suggest that activation of Lck by IL-2 may play a role in regulating CD3-mediated T cell functions. (C) 1995 Academic Press, Inc.