Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNF-alpha-mediated enhancement of T cell responses.
The expression of specific tumor necrosis factor (TNF) membrane receptors and biological effects of recombinant TNF (rTNF)-alpha on normal human T lymphocytes were studied. Although resting T cells lacked specific binding capacity for rTNF-alpha, high affinity (Kd 70 pM) TNF receptors were de novo induced upon primary activation of T cells. Comparison of TNF receptor expression with that of high affinity interleukin 2 (IL-2) and interferon-gamma (IFN-gamma) receptors, respectively, revealed similarities to IL 2-receptor expression with respect to kinetics of induction. However, maximum expression of TNF receptors (approximately equal to 5000/cell at day 6) and subsequent decline occurred approximately 3 days after the peak of IL 2-receptor expression. In contrast, no change in the expression of IFN-gamma receptors (Kd 10 pM, 300 to 400 receptors/cell) was found in the course of T cell activation. On activated TNF receptor positive T cells, TNF-alpha exerted multiple stimulatory activities. Thus TNF increased the expression of HLA-DR antigens and high affinity IL 2 receptors. As a consequence, TNF-treated T cells showed an enhanced proliferative response to IL 2. Moreover, TNF-alpha was effective as a co-stimulator of IL 2-dependent IFN-gamma production. These data indicate that TNF-alpha may regulate growth and functional activities of normal T cells.
D006023:Glycoproteins / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation; D011956:Receptors, Cell Surface / Q000502:physiology*; D011971:Receptors, Immunologic / Q000276:immunology / Q000502:physiology; D017471:Receptors, Interferon; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D006684:HLA-DR Antigens; D007376:Interleukin-2; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma