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The interleukin (IL)-12 receptor (R)β2 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)-γ play separate, but complementary, roles in regulating IL-12Rβ2 expression on antigen-specific CD4 + T cells. These results are consistent with our previous observation that IL-12 can promote autoimmune disease through IFN-γ–independent as well as –dependent pathways. Therefore, we compared the induction of IL-12 by, and the expression of the IL-12Rβ2 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-12Rβ2 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-12Rβ2 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-12Rβ2 subunit may be useful for the treatment of autoimmune diseases. autoimmunity experimental allergic encephalomyelitis T helper cell type 1 lymphocytes interferon γ CD40 ligand Footnotes J.T. Chang is a Research Scholar of the Howard Hughes Medical Institute. Abbreviations used in this paper: CD40L CD40 ligand CIA collagen- induced arthritis EAE experimental allergic encephalomyelitis MBP myelin basic protein NP nucleoprotein PLP proteolipid protein Submitted: 20 November 1998 Revision received 25 January 1999
The Journal of Experimental Medicine – Rockefeller University Press
Published: Mar 15, 1999
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