γδ T cells regulate the extent and duration of inflammation in the central nervous system by a Fas ligand-dependent mechanism
γδ T cells regulate the extent and duration of inflammation in the central nervous system by a Fas ligand-dependent mechanism
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DOI：
10.4049/jimmunol.174.8.4678
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发表时间：
2005-04-15
影响因子：
4.4
通讯作者：
Dittel, BN
中科院分区：
文献类型：
--
作者：
Ponomarev, ED;Dittel, BN
γ δ T细胞已被证明可以调节与炎症相关的免疫反应，但这种调节的机制在很大程度上是未知的。利用人类中枢神经系统自身免疫性疾病多发性硬化症的实验性自身免疫性脑脊髓炎（EAE）模型，我们证明γ δ T细胞是中枢神经系统炎症的重要调节因子。这在无法从EAE中恢复的γ δ T细胞缺陷小鼠身上得到了证明。慢性疾病伴随着巨噬细胞和淋巴细胞在中枢神经系统的长期存在。这种延长的炎症反应是由于细胞增殖和死亡的改变。在缺乏γ δ T细胞的小鼠中，与EAE恢复后的对照组小鼠相比，脑源性T细胞的增殖增加了3倍，而表明细胞凋亡的caspase活性降低了2倍。用野生型γ δ T细胞重组的γ δ T细胞缺陷小鼠从EAE中恢复并解决了中枢神经系统的炎症，而用Fas配体功能失调的γ δ T细胞重组的小鼠则没有。因此，伽马δ T细胞通过Fas/Fas配体诱导的脑源性T细胞凋亡来调节中枢神经系统的炎症和疾病恢复，快速解决中枢神经系统的炎症对于防止中枢神经系统永久性损伤导致慢性疾病至关重要。
gamma delta T cells have been shown to regulate immune responses associated with inflammation, but the mechanism of this regulation is largely unknown. Using the experimental autoimmune encephalomyelitis (EAE) model of the human CNS autoimmune disease multiple sclerosis, we demonstrate that gamma delta T cells are important regulators of CNS inflammation. This was shown using gamma delta T cell-deficient mice that were unable to recover from EAE. The chronic disease was accompanied by a prolonged presence of both macrophages and lymphocytes in the CNS. This extended inflammatory response was due to alterations in both cell proliferation and death. In mice lacking gamma delta T cells, proliferation of encephalitogenic T cells was 3-fold higher, and caspase activity, indicating apoptosis, was 2-fold lower compared with those in control mice recovering from EAE. gamma delta T cell-deficient mice reconstituted with wild-type gamma delta T cells recovered from EAE and resolved inflammation in the CNS, whereas mice reconstituted with Fas ligand-dysfunctional gamma delta T cells did not. Thus, gamma delta T cells regulate both inflammation in the CNS and disease recovery via Fas/Fas ligand-induced apoptosis of encephalitogenic T cells, and a quick resolution of inflammation in the CNS is essential to prevent permanent damage to the CNS resulting in chronic disease.