Expression of the Gene for Tumor Necrosis Factor-β but Not for Tumor Necrosis Factor-α Is Impaired in Tumor-Bearing Mice

Spleen cells from mice bearing progressively growing syngeneic sarcomas are immunologically hyporeactive and respond by significantly decreased proliferative response to stimulation with mitogens and cytokines. Here we show that these hyporeactive cells synthesize, after mitogen stimulation, comparable amount of mRNA for tumor necrosis factor (TNF)-α as do cells from control mice. However, stimulated spleen cells from the same tumor-bearing mice produce considerably less mRNA for TNF-β than cells from control mice. These observations were further confirmed using purified peritoneal macrophages and enriched splenic T cells. The results thus demonstrate a distinct regulation of expression of genes for TNF-α and TNF-β two functionally very similar cytokines, and simultaneously a selective impairment of T-cell function in the course of growth of syngeneic tumors in mice.