Regulation of interleukin (IL)-12 receptor beta2 subunit expression by endogenous IL-12: a critical step in the differentiation of pathogenic autoreactive T cells.
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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DOI：
10.1084/jem.189.6.969
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发表时间：
1999-03-15
期刊：
影响因子：
--
通讯作者：
Segal BM
中科院分区：
文献类型：
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作者：
Chang JT;Shevach EM;Segal BM
白细胞介素(IL)-12受体(R)β2亚基是参与维持IL-12反应性和控制T辅助细胞1型谱系承诺的关键分子。我们证明IL-12和干扰素(IFN)-γ在调节抗原特异性CD4+ T细胞上IL-12Rβ2表达方面发挥着独立但互补的作用。这些结果与我们之前的观察一致，即IL-12可以通过IFN-γ非依赖性和-依赖性途径促进自身免疫性疾病。因此，我们比较了实验性过敏性脑脊髓炎（EAE）易感的SJL （H-2s）小鼠和EAE耐药的B10小鼠髓鞘碱性蛋白（MBP）特异性T细胞对IL-12的诱导和IL-12Rβ2亚基在髓鞘碱性蛋白（MBP）特异性T细胞上的表达。S小鼠（H-2s）。B10。S小鼠在上调IL-12Rβ2亚基的能力上存在抗原特异性缺陷。缺陷表达不是继发于抑制性细胞因子的产生，而是源于B10的失败。S mbp特异性T细胞上调CD40配体表达并诱导IL-12的产生。IL-12的加入可以恢复这些细胞IL-12Rβ2的表达和脑致生能力。这些结果表明，针对IL-12Rβ2亚基的免疫疗法的发展可能有助于治疗自身免疫性疾病。
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-2s) mice and from EAE- resistant B10.S mice (H-2s). 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.