Effects of IL-12 on the generation of cytotoxic activity in human CD8 super(+) T lymphocytes

We have studied the effects of human rIL-12 on the proliferation and generation of cytotoxic activity in human CTL precursors. Purified human blood CD8 super(+) T lymphocytes were stimulated overnight with immobilized alpha -CD3 and cultured 3 to 4 additional days under various conditions. The addition of IL-12 resulted in a marked (10- to 20-fold), dose-dependent, augmentation of cytotoxicity per cell with a smaller (2-fold) increase in cell number. IL-12 augmentation of proliferation and cytotoxicity of CD8 super(+) T cells was not inhibited by a mAb to the p55 subunit of the IL-2 receptor ( alpha -Tac) at a concentration sufficient to block the activity of exogenously added IL-2, indicating that the activity of IL-12 did not require IL-2. The broad set of potent effects of IL-12 on CD8 super(+) T cell responses suggests that IL-12 may play an important immunoregulatory role on CTL development in vivo and may be a useful tool for manipulating this process in vivo for investigational and immunotherapeutic purposes.