Regulation of CD8+ regulatory T cells: Interruption of the NKG2A-Qa-1 interaction allows robust suppressive activity and resolution of autoimmune disease
Regulation of CD8+ regulatory T cells: Interruption of the NKG2A-Qa-1 interaction allows robust suppressive activity and resolution of autoimmune disease
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DOI：
10.1073/pnas.0810383105
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发表时间：
2008-12-09
影响因子：
11.1
通讯作者：
Cantor, Harvey
中科院分区：
文献类型：
--
作者：
Lu, Linrong;Kim, Hye-Jung;Cantor, Harvey
调节自身反应性的CD4T细胞对于维持自身耐受性和预防自身免疫性疾病至关重要。尽管CD8T调节(Treg)细胞识别QA-1(人类的人类白细胞抗原-E)限制的自身多肽，抑制自身反应性的CD4细胞，并减轻实验性自身免疫性脑脊髓炎(EAE)，但这种相互作用的机制尚不清楚。我们产生了Qa-1突变敲入鼠，它损害了Qa-1与T细胞受体(TCR)和CD94/NKG2A受体的结合。对这些小鼠的分析表明，依赖于TCR的QA-1-肽复合体对靶CD4细胞的识别对于CD8 Treg细胞的抑制是必不可少的。进一步的分析表明，QA-1-CD94/NKG2A相互作用的遗传破坏释放了强大的CD8 Treg细胞活性，完全消除了EAE的发展。
Regulation of autoreactive CD4 T cells is essential to maintain self-tolerance and prevent autoimmune disease. Although CD8 T regulatory (Treg) cells that recognize self-peptides restricted by Qa-1 (HLA-E in humans) inhibit autoreactive CD4 cells and attenuate experimental autoimmune encephalomyelitis (EAE), the mechanism of this interaction is unclear. We generated Qa-1 mutant knock-in mice that impair Qa-1 binding to the T cell receptor (TCR) and CD94/NKG2A receptors. Analysis of these mice showed that TCR-dependent recognition of Qa-1-peptide complexes on target CD4 cells is essential for suppression by CD8 Treg cells. Further analysis revealed that genetic disruption of the Qa-1-CD94/NKG2A interaction unleashes robust CD8 Treg cell activity that completely abolishes development of EAE.