Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation
Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation
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DOI：
10.1038/nm1564
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发表时间：
2007-04-01
期刊：
影响因子：
82.9
通讯作者：
Kuchroo, Vijay K.
中科院分区：
文献类型：
--
作者：
Korn, Thomas;Reddy, Jayagopala;Kuchroo, Vijay K.
用离体产生的调节性T细胞（T-reg）治疗自身免疫性疾病已被认为是一种潜在的有吸引力的治疗方法。然而，T-reg在自身免疫中的动力学和功能尚不清楚。因此，我们开发了Foxp 3gfp敲入（Foxp3gfp.KI）小鼠和髓鞘少突胶质细胞糖蛋白（MOG）（35-55）/IA（B）（MHC II类）四聚体，以在实验性自身免疫性脑脊髓炎（EAE）（多发性硬化症的动物模型）期间体内追踪自身抗原特异性效应T细胞（T-eff）和T-reg。MOG四聚体反应性Foxp 3（+）T-reg在外周淋巴隔室中扩增，并容易在中枢神经系统（CNS）中积累，但不能阻止疾病的发作。从CNS分离的Foxp 3（+）T细胞有效抑制幼稚MOG特异性T细胞，但不能控制分泌白细胞介素（IL）-6和肿瘤坏死因子（TNF）的CNS衍生的致脑炎性T-eff。我们的数据表明，为了使CD 4（+）Foxp 3（+）T-reg有效地控制靶器官中的自身免疫反应，可能还需要控制组织炎症。
Treatment with ex vivo-generated regulatory T cells (T-reg) has been regarded as a potentially attractive therapeutic approach for autoimmune diseases. However, the dynamics and function of T-reg in autoimmunity are not well understood. Thus, we developed Foxp3gfp knock-in (Foxp3gfp.KI) mice and myelin oligodendrocyte glycoprotein (MOG)(35-55)/IA(b) (MHC class II) tetramers to track autoantigen-specific effector T cells (T-eff) and T-reg in vivo during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. MOG tetramer-reactive, Foxp3(+) T-reg expanded in the peripheral lymphoid compartment and readily accumulated in the central nervous system (CNS), but did not prevent the onset of disease. Foxp3(+) T cells isolated from the CNS were effective in suppressing naive MOG-specific T cells, but failed to control CNS-derived encephalitogenic T-eff that secreted interleukin (IL)-6 and tumor necrosis factor (TNF). Our data suggest that in order for CD4(+)Foxp3(+) T-reg to effectively control autoimmune reactions in the target organ, it may also be necessary to control tissue inflammation.