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.
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GE
Department of Molecular Biology and Immunology, Genentech, Inc., South San Francisco, California 94080.
Zlotnik
A
A
Espevik
T
T
Dinarello
C A
CA
Cerami
A
A
Palladino
M A
MA
D000818:Animals; D001688:Biological Products / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines; D004357:Drug Synergism; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D010835:Phytohemagglutinins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D001688:Biological Products; D016207:Cytokines; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha