IFN-γ- and IL-10-expressing virus epitope-specific Foxp3(+) T reg cells in the central nervous system during encephalomyelitis.
IFN-γ- and IL-10-expressing virus epitope-specific Foxp3(+) T reg cells in the central nervous system during encephalomyelitis.
复制标题
脑脊髓炎期间，中枢神经系统中的IFN-γ-和IL-10表达病毒表位特异性FOXP3（+）T reg细胞。
DOI：
10.1084/jem.20110236
复制
发表时间：
2011-08-01
期刊：
影响因子：
--
通讯作者：
Perlman S
中科院分区：
文献类型：
--
作者：
Zhao J;Zhao J;Fett C;Trandem K;Fleming E;Perlman S
病原体特异性Foxp3+ T reg细胞可以根据细胞因子的产生进行鉴定，可以在幼稚T细胞群中检测到，并且对具有相同抗原特异性的效应T细胞表现出抑制能力。Foxp3+ CD4调节性T细胞（T reg细胞）在限制感染的免疫病理中起重要作用。然而，鉴定这些细胞靶向的病原体特异性表位一直是难以捉摸的。利用MHC II类/肽四聚体和细胞内细胞因子染色，我们在冠状病毒感染的中枢神经系统和幼稚T细胞前体池中鉴定了识别两种病毒特异性CD4 T细胞表位的T细胞。这些T regg细胞与效应T细胞（T - eff细胞）同时被检测到，具有相同的特异性，并且在同源肽刺激后可以抑制T - eff细胞的增殖。这些病毒特异性T细胞可能在感染高峰期，当病毒抗原最大时，在抑制免疫反应方面特别有效。此外，这些T细胞在肽刺激后同时表达IL-10和IFN-γ。IFN-γ的表达在感染的急性和慢性阶段都保持不变。由于实验性自身免疫性脑脊髓炎小鼠的髓鞘少突胶质细胞糖蛋白特异性Foxp3+ T reg细胞在疾病高峰期表达IL-10和IL-17，因此通过细胞因子产生来鉴定T reg细胞靶表位也适用于自身免疫性疾病。这些结果表明，病原体表位特异性Foxp3+ T regg细胞可以根据细胞因子的产生进行鉴定。
Pathogen-specific Foxp3+ T reg cells can be identified on the basis of cytokine production, are detected in naive T cell populations, and exhibit suppressive ability toward effector T cells with the same antigen specificity. Foxp3+ CD4 regulatory T cells (T reg cells) are important in limiting immunopathology in infections. However, identifying pathogen-specific epitopes targeted by these cells has been elusive. Using MHC class II/peptide tetramers and intracellular cytokine staining, we identify T reg cells recognizing two virus-specific CD4 T cell epitopes in the coronavirus-infected central nervous system as well as naive T cell precursor pools. These T reg cells are detected at the same time as effector T cells (T eff cells) exhibiting the same specificity and can suppress T eff cell proliferation after stimulation with cognate peptide. These virus-specific T reg cells may be especially effective in inhibiting the immune response during the peak of infection, when virus antigen is maximal. Furthermore, these T reg cells express both IL-10 and IFN-γ after peptide stimulation. IFN-γ expression is maintained during both acute and chronic phases of infection. Identification of T reg cell target epitopes by cytokine production is also applicable in autoimmune disease because myelin oligodendrocyte glycoprotein–specific Foxp3+ T reg cells express IL-10 and IL-17 at the peak of disease in mice with experimental autoimmune encephalomyelitis. These results show that pathogen epitope-specific Foxp3+ T reg cells can be identified on the basis of cytokine production.