Does the frequency and avidity spectrum of the neuroantigen-specific T cells in the blood mirror the autoimmune process in the central nervous system of mice undergoing experimental allergic encephalomyelitis?
Does the frequency and avidity spectrum of the neuroantigen-specific T cells in the blood mirror the autoimmune process in the central nervous system of mice undergoing experimental allergic encephalomyelitis?
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DOI：
10.4049/jimmunol.174.8.4598
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发表时间：
2005-04-15
影响因子：
4.4
通讯作者：
Lehmann, PV
中科院分区：
文献类型：
--
作者：
Hofstetter, HH;Targoni, OS;Lehmann, PV
在人类中，对介导多发性硬化的自身反应性T细胞的研究主要局限于检测外周血淋巴细胞。很少有人知道这些测量是如何反映中枢神经系统中介导疾病的自身反应性T细胞的。这一信息也不适用于小鼠实验性过敏性脑脊髓炎（EAE）；从小鼠的血液或大脑中获得的T细胞数量很少，因此无法进行这种比较。我们使用单细胞分辨率ifn - γ ELISPOT测定了用该肽免疫SJL小鼠的髓鞘碱性蛋白（MBP:87-99）特异性CD4细胞的频率和功能活性。功能性MBP：在EAE的临床症状期间，中枢神经系统中存在87-99特异性ifn - γ产生细胞，但在恢复期不存在。相比之下，MBP:87-99特异性T细胞在疾病的所有阶段都持续存在于血液中，并且在未发生EAE的小鼠中也存在。因此，血液中MBP:87-99反应性T细胞频率的增加可靠地反映了启动状态，而不是大脑中这些细胞的炎症活性。脑和血液中MBP:87-99反应性T细胞的功能活性是相同的，并且在小鼠从急性到慢性EAE进展的2个月内没有变化。因此，高亲和力T细胞在靶器官中没有选择性富集，MBP:87-99特异性T细胞库的快速成熟在观察期间没有发生。这些数据可能有助于解释多发性硬化症患者外周血淋巴细胞的测量结果。
In humans, studies of autoreactive T cells that mediate multiple sclerosis have been largely confined to testing peripheral blood lymphocytes. Little is known how such measurements reflect the disease-mediating autoreactive T cells in the CNS. This information is also not available for murine experimental allergic encephalomyelitis (EAE); the low number of T cells that can be obtained from the blood or the brain of mice prevented such comparisons. We used single-cell resolution IFN-gamma ELISPOT assays to measure the frequencies and functional avidities of myelin basic protein (MBP:87-99)-specific CD4 cells in SJL mice immunized with this peptide. Functional MBP:87-99-specific IFN-gamma-producing cells were present in the CNS during clinical signs of EAE, but not during phases of recovery. In contrast, MBP:87-99-specific T cells persisted in the blood during all stages of the disease, and were also present in mice that did not develop EAE. Therefore, the increased frequency of MBP:87-99-reactive T cells in the blood reliably reflected the primed state, but not the inflammatory activity of these cells in the brain. The functional avidity of the MBP:87-99-reactive T cells was identical in the brain and blood and did not change over 2 mo as the mice progressed from acute to chronic EAE. Therefore, high-affinity T cells did not become selectively enriched in the target organ, and avidity maturation of the MBP:87-99-specific T cell repertoire did not occur in the observation period. The data may help the interpretation of measurements made with peripheral blood lymphocytes of multiple sclerosis patients.