Tumor necrosis factor alpha/cachectin is a growth factor for thymocytes. Synergistic interactions with other cytokines

Recombinant murine (rm) TNF-alpha but not recombinant human (rh) TNF- alpha induces the proliferation of murine thymocytes in the presence of a comitogenic stimulus. This effect does not appear to be due to the production of significant levels of IL-1, IL-2, or IL-4. although not directly mitogenic (i.e., in the absence of PHA-P) for thymocytes, rmTNF-alpha amplifies the direct mitogenic signals from hIL-1 and rhIL- 2 but not rmIL-4. In the presence of PHA-P, thymocytes stimulated with hIL-1, rhIL-2, and rmIL-4 produced significant amounts of TNF-alpha. Although rhTNF-alpha does not induce a proliferative response, it will competitively inhibit the proliferative response of thymocytes to rmTNF- alpha. These data suggest a critical role for TNF-alpha in the intrathymic proliferation of developing T cells.