Tumor necrosis factor-alpha and interleukin 6 synergistically induce T cell growth.

T cells stimulated with phytohemagglutinin are dependent on monocyte-derived helper signals (e.g. interleukin (IL) 6 and IL 1) for their proliferation. In the present study the effect of recombinant tumor necrosis factor alpha (rTNF-alpha) as a helper signal for growth of highly purified peripheral blood human T cells stimulated with phytohemagglutinin was examined. TNF-alpha alone had a weak co-stimulatory effect, while a combination of TNF-alpha and IL 6 provided highly effective synergistic helper signals for T cell proliferation. The effect of TNF-alpha could not be ascribed to secondary induction of IL 1 production. The effect of TNF-alpha on T cell proliferation was also found to be independent of the autocrine T cell growth factors IL 2 and IL 4. This latter points to dissimilarity between IL 1 and TNF-alpha in the mechanism by which each of these two cytokines in combination with IL 6 promotes T cell proliferation. TNF-alpha, IL 6 and IL 1 thus seem to follow different pathways in their function as helper signals in T cell activation.