Regulatory T cells in experimental allergic encephalomyelitis. I. Frequency and specificity analysis in normal and immune rats of a T cell subset that inhibits disease.
Regulatory T cells in experimental allergic encephalomyelitis. I. Frequency and specificity analysis in normal and immune rats of a T cell subset that inhibits disease.
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实验性过敏性脑脊髓炎中的调节性 T 细胞。
DOI：
10.1093/intimm/11.3.307
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发表时间：
1999
影响因子：
4.4
通讯作者：
Wilson,DB
中科院分区：
文献类型：
--
作者：
Sun,D;Whitaker,JN;Wilson,DB
我们以前已经表明，髓鞘碱性蛋白（MBP）反应性T细胞给药幼稚刘易斯大鼠不仅诱导自身免疫性脑脊髓炎（EAE），但也几乎完全抵抗随后的疾病。通过分离负责抗性的效应细胞，我们证明了疾病保护与CD8+调节性T细胞（RTC）亚群数量的增加有关，并且该RTC亚群与致脑炎T细胞的共注射中止了后者细胞的致病活性。在这里，我们表明，一个放射敏感的脾脏RTC人口也存在于幼稚大鼠，可以招募和激活，以抑制继发性EAE的发病。在共转移实验中，这种保护性RTC亚群可以被分离出来，以中和体内刺激性MBP反应性T细胞的致病活性。我们发现，在幼稚大鼠的频率与特异性MBP反应性T细胞的RTC是两个数量级高于MBP特异性前体的频率，RTC的活性随着年龄的增长和RTC的频率增加，作为一个结果与MBP反应性细胞系免疫。在特异性研究中，我们表明，从幼稚大鼠和RTC从动物与一个MBP反应性细胞系引发的RTC分离显示交叉反应性反应，以各种不同的MBP反应性T细胞系。然而，在用给定的MBP系重复刺激后，这些RTC显示出对选择系的更有限的克隆型应答，并呈现出均匀的CD8表型。最后，RTC的功能研究表明，增殖和裂解特异性不一定相关，激活的大鼠RTC是特别裂解的Fas敏感的鼠细胞系。
We have shown previously that administration of myelin basic protein (MBP)-reactive T cells to naive Lewis rats induces not only autoimmune encephalomyelitis (EAE) but also a near total resistance to subsequent disease. By isolating the effector cells that are responsible for the resistance, we demonstrated that disease protection paralleled with increased numbers of a CD8+regulatory T cell (RTC) subset and that co-injection of this RTC subset with encephalitogenic T cells aborted the pathogenic activity of the latter cells. Here, we show that a radio-sensitive splenic population of RTC also exists in naive rats that can be recruited and activated to inhibit the onset of secondary episodes of adoptive EAE. In co-transfer experiments, this protective RTC subpopulation can be isolated to neutralize the pathogenic activity of stimulatory MBP-reactive T cellsin vivo. We show that the frequency of RTC with specificity for MBP-reactive T cells in naive rats is two orders of magnitude higher than the frequency of MBP-specific precursors, the activity of RTC increases substantially with age and RTC frequencies increase as a consequence of immunization with MBP-reactive cells lines. In specificity studies, we show that RTC isolated from naive rats and RTC from animals primed with one MBP-reactive cell line show cross-reactive responses to a variety of different MBP-reactive T cell lines. However, following repeated stimulation with a given MBP line, these RTC display a more limited, clonotypic response to the selecting line and assume a uniform CD8 phenotype. Finally, functional studies with RTC indicate that proliferative and lytic specificities do not necessarily correlate and that activated rat RTC are especially lytic for a Fas-sensitive murine cell line.