Regulation of autoimmune diabetes by non-isletspecific T cells - a role for the glucocorticoidinduced TNF receptor
Regulation of autoimmune diabetes by non-isletspecific T cells - a role for the glucocorticoidinduced TNF receptor
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DOI：
10.1002/eji.200324599
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发表时间：
2004-02-01
影响因子：
5.4
通讯作者：
Kanagawa, O
中科院分区：
文献类型：
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作者：
Suri, A;Shimizu, J;Kanagawa, O
当将致糖尿病的 BDC2.5 CD4 T 细胞注射到 NOD.scid 小鼠体内时，会诱发糖尿病。然而，当与 OVA 特异性 DO11.10CD4 T 细胞共转移时，BDC2.5 T 细胞未能引起糖尿病。这种抑制依赖于仅用可溶性 OVA 刺激 DO11.10 T 细胞，这使得它们在体内分化为 Th2 型细胞因子分泌模式。然而，使用单克隆抗体体内中和IL-4、IL-10或TGF-β并不能阻止抑制作用，而用抗糖皮质激素诱导的TNF受体的抗体治疗则消除了对疾病的保护作用。在受保护的小鼠中，可以从其脾脏中分离出致糖尿病 T 细胞，并将其注射到新的 NOD.scid 受体中时，可以转移糖尿病。因此，抑制作用的发生并没有物理或功能性地消除致糖尿病T细胞。
Diabetogenic BDC2.5 CD4 T cells induce diabetes when injected into NOD.scid mice. However, when co-transferred with the OVA-specific DO11.10CD4 T cells, BDC2.5 T cells failed to cause diabetes. This inhibition depended upon the stimulation of DO11.10 T cells only with soluble OVA, which skewed their differentiation to a Th2-type pattern of cytokine secretion in vivo. However, in vivo neutralization of IL-4, IL-10 or TGF-beta using monoclonal antibodies did not prevent the inhibition whereas treatment with an antibody against the glucocorticoid-induced TNF receptor abrogated the protection from disease. In the protected mice, the diabetogenic T cells could be isolated from their spleens and shown to transfer diabetes when injected into new NOD.scid recipients. Thus, the inhibition took place without the physical or functional elimination of the diabetogenic T cells.