Regulation of interleukin (IL)-12 receptor beta2 subunit expression by endogenous IL-12: a critical step in the differentiation of pathogenic autoreactive T cells.
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| Abstract |
The interleukin (IL)-12 receptor (R)beta2 subunit is the critical molecule involved in maintaining IL-12 responsiveness and controlling T helper cell type 1 lineage commitment. We demonstrate that IL-12 and interferon (IFN)-gamma play separate, but complementary, roles in regulating IL-12Rbeta2 expression on antigen-specific CD4(+) T cells. These results are consistent with our previous observation that IL-12 can promote autoimmune disease through IFN-gamma-independent as well as -dependent pathways. Therefore, we compared the induction of IL-12 by, and the expression of the IL-12Rbeta2 subunit on, myelin basic protein (MBP)-specific T cells from experimental allergic encephalomyelitis (EAE)-susceptible SJL (H-2(s)) mice and from EAE- resistant B10.S mice (H-2(s)). B10.S mice had an antigen-specific defect in their capacity to upregulate the IL-12Rbeta2 subunit. Defective expression was not secondary to the production of suppressive cytokines, but to a failure of B10.S MBP-specific T cells to upregulate CD40 ligand expression and to induce the production of IL-12. IL-12Rbeta2 expression as well as encephalitogenicity of these cells could be restored by the addition of IL-12. These results suggest that the development of immunotherapies that target the IL-12Rbeta2 subunit may be useful for the treatment of autoimmune diseases.
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| Authors | J T Chang, E M Shevach, B M Segal |
| Journal | The Journal of experimental medicine (J Exp Med) Vol. 189 Issue 6 Pg. 969-78 (Mar 15 1999) ISSN: 0022-1007 [Print] United States |
| PMID | 10075980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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