Role of IL-6, IL-2, and IL-4 in the in vitro induction of cytotoxic T cells.

The mode of IL-6-induced differentiation of Con A-stimulated CD4-CD8+ CTL-P was examined. Through application of neutralizing anti-IL-6, anti-IL-2, and anti-IL-4 mAb it was shown that IL-6 is an "early acting" factor for development of accessory cell-depleted thymocytes. IL-2 and IL-4 are obligatory "late acting" factors for this process. In accordance IL-4, but not IL-6, induced active CTL from CD4-CD8+ CTL-P. The increase of CD4-CD8+ CTL originates at least partially from CD4+CD8+ cells differentiating to active CTL in vitro. CTL development was paralleled by an increase in CD4-CD8+ cells and by a distinct increase in [3H]TdR uptake on day 2 of cultivation. Our data suggest that IL-6 induces Th cells to produce IL-2 and IL-4, the mediators for final differentiation of CD4-CD8+ cells.