Arthritogenic Self-Reactive CD4+ T Cells Acquire an FR4hi CD73hi Anergic State in the Presence of Foxp3+ Regulatory T Cells
Arthritogenic Self-Reactive CD4+ T Cells Acquire an FR4hi CD73hi Anergic State in the Presence of Foxp3+ Regulatory T Cells
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DOI：
10.4049/jimmunol.1101311
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发表时间：
2012-01-01
影响因子：
4.4
通讯作者：
Mueller, Daniel L.
中科院分区：
文献类型：
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作者：
Martinez, Ryan J.;Zhang, Na;Mueller, Daniel L.
类风湿性关节炎的发生与外周CD4(+) T细胞内稳态的缺陷有关。T细胞淋巴细胞减少也已被证明是诱导CD4(+) T细胞克隆无能的一个障碍。因此，我们通过追踪在选择性T细胞淋巴细胞减少情况下葡萄糖 - 6 - 磷酸异构酶（GPI）反应性CD4(+) T细胞的命运，来探究克隆无能诱导与自身免疫性关节炎避免之间的关系。在正常小鼠宿主中，CD4(+) T细胞对自身GPI肽/主要组织相容性复合体II类复合物的识别不会导致关节炎，而是使这些T细胞发展出叶酸受体4(高)CD73(高)的无能表型。相反，选择性去除多克隆Foxp3(+)CD4(+)调节性T细胞的宿主不能使GPI特异性CD4(+) T细胞产生无能，并且无法控制关节炎。这表明当Foxp3(+)CD4(+)调节性T细胞不足以使所有遇到自身抗原的自身反应性CD4(+) T细胞功能性失活时，在淋巴细胞减少的情况下会发生自身免疫性关节炎。《免疫学杂志》，2012年，188卷：170 - 181页。
Rheumatoid arthritis develops in association with a defect in peripheral CD4(+) T cell homeostasis. T cell lymphopenia has also been shown to be a barrier to CD4(+) T cell clonal anergy induction. We therefore explored the relationship between clonal anergy induction and the avoidance of autoimmune arthritis by tracking the fate of glucose-6-phosphate isomerase (GPI)-reactive CD4(+) T cells in the setting of selective T cell lymphopenia. CD4(+) T cell recognition of self-GPI peptide/MHC class II complexes in normal murine hosts did not lead to arthritis and instead caused those T cells to develop a Folate receptor 4(hi)CD73(hi) anergic phenotype. In contrast, hosts selectively depleted of polyclonal Foxp3(+)CD4(+) regulatory T cells could not make GPI-specific CD4(+) T cells anergic and failed to control arthritis. This suggests that autoimmune arthritis develops in the setting of lymphopenia when Foxp3(+)CD4(+) regulatory T cells are insufficient to functionally inactivate all autoreactive CD4(+) T cells that encounter selfAg. The Journal of Immunology, 2012, 188: 170-181.