| Functional interaction between TGF-beta and IL-12 in human primary allogeneic cytotoxicity and proliferative response. | |
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MedLine Citation:
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PMID: 8977184 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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IL-12 is an important cytokine in the control of cell-mediated immunity. We have investigated the functional interaction of IL-12 with TGF-beta1, a cytokine involved in the regulation of growth and differentiation of immunocompetent cells, during human allogeneic response development. Using primary MLR, our data show that addition of exogenous TGF-beta at the sensitizing phase of the primary MLR resulted in the inhibition of both allogeneic cytotoxic and proliferative responses. The inhibitory effect of TGF-beta on allogeneic response involves an abrogation of IL-12/p70 production upon allostimulation. In contrast to its effect on IL-12 production, TGF-beta did not alter the expression of IL-12R beta1-chain (IL-12R beta) in T cells induced upon allogeneic activation. Addition of exogenous IL-12 or IFN-gamma in the MLR cultures in the presence of TGF-beta did not result in reversal of CTL generation and T cell proliferation. Interestingly, TGF-beta was efficient in down-regulating IL-12 responsiveness of alloactivated T cells as well as TCR-alphabeta or TCR-gammadelta alloreactive T cell clones. These studies suggest that the inhibitory effect of TGF-beta on the development of human allogeneic proliferation and cytotoxic responses involves an additional mechanism associated with an interference with IL-12 pathway. |
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Authors:
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C Pardoux; C Asselin-Paturel; J Chehimi; F Gay; F Mami-Chouaib; S Chouaib |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 158 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 1997 Jan |
Date Detail:
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Created Date: 1997-01-30 Completed Date: 1997-01-30 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 136-43 Citation Subset: AIM; IM |
Affiliation:
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Laboratory of Cytokines and Antitumor Immunity, CJF 94-11 INSERM, Gustave Roussy Institute, Villejuif, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Cytotoxicity, Immunologic / drug effects* Drug Synergism Humans Interferon-gamma / biosynthesis, drug effects Interleukin-12 / pharmacology* Isoantigens / immunology* Lymphocyte Activation / drug effects* Lymphocyte Culture Test, Mixed Receptors, Interleukin / biosynthesis, drug effects T-Lymphocytes, Cytotoxic / drug effects*, metabolism Transforming Growth Factor beta / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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AI34758/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Isoantigens; 0/Receptors, Interleukin; 0/Transforming Growth Factor beta; 187348-17-0/Interleukin-12; 82115-62-6/Interferon-gamma |
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