Contribution of p56 lck to the upregulation of cytokine production and T cell proliferation by IL-2 in human CD3-stimulated T cell clones

Abstract

Interaction of the interleukin 2 receptor (IL-2R) β chain with the lymphocyte-specific protein tyrosine kinase (PTK), p56 lck, has led to the speculation that p56 lck participates in growth signal transduction. Although activation of T cells with interleukin 2 (IL-2) results in the activation of p56 lck, accumulating data support the notion that Lck does not play an essential role in mitogenic signal delivery from the IL-2R. Since this src-related PTK has been shown to enhance TCR/CD3-mediated T cell responsiveness, here we investigated whether activation 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 cytokine production. Results show that p56 lck kinase activity increased as early as 1 min, reached a maximum within 5 min and decreased 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-γ secretion and by T cell proliferation. This increase of T cell functions was correlated with IL-2-induced p56 lck activation in both dose—response and time—course experiments. Taken together these results strongly suggest that activation of Lck by IL-2 may play a role in regulating CD3-mediated T cell functions.