Comparative effects of tumor necrosis factor-α and IL-1β on mitogen-induced T cell activation

The effect of rTNF-α on human T cell function was examined and compared with that of rIL-1β by assessing the ability of each cytokine to support mitogen-induced proliferation, IL-2 production, and IL-2R expression. TNF-α and IL-1β each enhanced DNA synthesis induced by PHA or immobilized mAb to the CD3 molecular complex. In addition, each cytokine increased the number of cells entering the G₁ phase of the cell cycle and augmented IL-2R expression. The combination of optimal concentrations of these factors supported these responses to a greater extent than either cytokine alone, suggesting that T cell responsiveness is independently regulated by the action of at least two separate monocyte derived cytokines. Whereas TNF-α had little effect, IL-1β augmented IL-2 mRNA expression and IL-2 production by mitogen-stimulated cells. Furthermore, IL-1β enhanced proliferation with increasing length of culture. Whereas TNF-α also enhanced proliferation late in culture, it was less effective in this regard than IL-1β. Thus, IL-1β and TNF-α augment mitogen-induced T cell proliferation by increasing the number of cells initially activated and by promoting subsequent cell cycle progression. They differ, however, in their capacity to promote IL-2 mRNA and IL-2 production and therefore ongoing T cell proliferation.