1. Glutathione (GSH) regulation of the CD3-AK response. GSH, a tripeptide, up-regulates the differentiation of preactivated IL-2 dependent activated killer cells, namely LAK and CD3-AK. GSH acts through the up-regulation of the utilization of IL-2. In contrast, GSH down-regulates the generation of LAK and CD3-AK in resting T cells. Flow cytometry analysis reveals that GSH down-regulates the expression of IL-2 receptors and T cell receptor CD3 on the surface of activated killer cells. It appears that through this effect the activation of T cells in resting lymphocytes was suppressed. Therefore, GSH exerts a dichotomous effect on the regulation of the generation of activated killer cells. 2. Cytokine regulation of the generation of activated killer cells. The generation of CD3-AK is largely PKC (protein kinase C) dependent. After depleting PKC by prolonged treatment with PMA, splenocytes lost their ability to generate CD3-AK cells in culture, medium which was supplemented with IL-2. However, adding IL-4 in the cultures restored the responsiveness to alphaCD3 activation. Therefore, IL-4 appears to play a major role in a PKC-independent pathway for the generation of CD3-AK cells.
