Enhancement of antigen- and mitogen-induced human T lymphocyte proliferation by tumor necrosis factor-alpha.
The capacity of human recombinant tumor necrosis factor-alpha (rTNF alpha) to modulate human T cell proliferation was examined. To examine the effect of rTNF alpha on the responding T cell directly, T cell activation was studied in the absence of viable accessory cells (AC). Highly purified AC-depleted peripheral blood T4 or T8 cells were stimulated with immobilized monoclonal antibodies to the cluster of differentiation (CD)3 molecular complex, an AC-independent stimulus. rTNF alpha augmented anti-CD3-stimulated T4 and T8 cell proliferation. The capacity of rTNF alpha to enhance T cell proliferation varied inversely with the density of immobilized anti-CD3 and the number of responding cells in each culture. The capacity of rTNF alpha to enhance antigen-induced T4 cell proliferation was also examined. Antigen-bearing paraformaldehyde-fixed antigen-presenting cells induced modest T4 cell proliferation when cultured in flat-bottomed wells; this response was enhanced by rTNF alpha. The results demonstrate that rTNF alpha has direct effects on T cells, facilitating their capacity to proliferate in response to mitogens and antigens. These data indicate that rTNF alpha may play an immunoregulatory role, enhancing the proliferation of T lymphocytes.
Yokota
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S
Department of Internal Medicine, University of Texas Health Science Center, Dallas 75235.
Geppert
T D
TD
Lipsky
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PE
D000328:Adult; D000911:Antibodies, Monoclonal / Q000502:physiology; D000942:Antigens, Bacterial / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007166:Immunosuppressive Agents / Q000502:physiology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology; D008934:Mitogens / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000945:Antigens, Differentiation, T-Lymphocyte; D007166:Immunosuppressive Agents; D008934:Mitogens; D011994:Recombinant Proteins; D013745:Tetanus Toxoid; D014409:Tumor Necrosis Factor-alpha