Differential secretion of tumor necrosis factor-alpha and granulocyte/macrophage colony-stimulating factors but not interferon-gamma from CD4+ compared to CD8+ human T cell clones.

Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic lymphokine which may have important regulatory effects on immune responses. It is shown here that eight alloreactive CD4+ T cell clones (TCC) secreted significant amounts of TNF-alpha after stimulation with either specific alloantigen or 12-O-tetradecanoylphorbol 13-acetate together with the calcium ionophore ionomycin (up to 50 ng/ml/24 h/10(6) cells) whereas CD8+ TCC failed to do so (max. 2 ng/ml/24 h/10(6) cells). The CD8+ TCC also secreted markedly less granulocyte/macrophage colony-stimulating factor than the CD4+ cells. However, this was not indicative of a general decrease of lymphokine production by CD8+ cells because CD4+ and CD8+ TCC both secreted similar amounts of interferon-gamma. These results show that regulatory CD4+ lymphocytes can produce large amounts of TNF-alpha, whereas CD8+ effector cells cannot do so.