Effector-Memory T Cells Develop in Islets and Report Islet Pathology in Type 1 Diabetes
Effector-Memory T Cells Develop in Islets and Report Islet Pathology in Type 1 Diabetes
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DOI：
10.4049/jimmunol.1302100
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发表时间：
2014-01-15
影响因子：
4.4
通讯作者：
Krishnamurthy, Balasubramanian
中科院分区：
文献类型：
--
作者：
Chee, Jonathan;Ko, Hyun-Ja;Krishnamurthy, Balasubramanian
CD 8（+）T细胞在人类1型糖尿病和NOD小鼠中至关重要。在这项研究中，我们使用MHC-四聚体技术阐明了NOD糖尿病中胰岛特异性葡萄糖-6-磷酸酶催化亚基相关蛋白（IGRP）特异性CD 8（+）T细胞的自然史。外周淋巴组织中的FSG（206-214）特异性T细胞随着年龄的增长而增加，其数量与胰岛炎进展相关。在外周淋巴组织中的IGRP（206-214）特异性T细胞表达慢性Ag刺激的标志物，并且它们的数量在糖尿病诊断后稳定，与它们的记忆表型一致。NOD小鼠中的IGRP（206-214）特异性T细胞扩增，获得胰岛中的效应记忆T细胞的表型，并迁移到外周淋巴组织。我们的观察结果表明，计数效应记忆T细胞的多种自身抗原特异性的1型糖尿病患者外周血中可能是一个可靠的报告胰岛病理进展。
CD8(+) T cells are critical in human type 1 diabetes and in the NOD mouse. In this study, we elucidated the natural history of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific CD8(+) T cells in NOD diabetes using MHC-tetramer technology. IGRP(206-214)-specific T cells in the peripheral lymphoid tissue increased with age, and their numbers correlated with insulitis progression. IGRP(206-214)-specific T cells in the peripheral lymphoid tissue expressed markers of chronic Ag stimulation, and their numbers were stable after diagnosis of diabetes, consistent with their memory phenotype. IGRP(206-214)-specific T cells in NOD mice expand, acquire the phenotype of effector-memory T cells in the islets, and emigrate to the peripheral lymphoid tissue. Our observations suggest that enumeration of effector-memory T cells of multiple autoantigen specificities in the periphery of type 1 diabetic subjects could be a reliable reporter for progression of islet pathology.