Mannie M D, Watkins S L
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27858.
Immunol Lett. 1993 Nov;38(3):237-42. doi: 10.1016/0165-2478(93)90012-q.
T-cell hybridomas specific for myelin basic protein (MBP) were used to assess regulation of co-stimulatory signals during remission of experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Both THYB-1 and THYB-2 subsets of T-cell hybridomas recognize class II major histocompatibility complex-restricted determinants in the 72-86 encephalitogenic region of MBP. However, THYB-2 hybrids uniquely express additional requirements for co-stimulatory signals from radiosensitive splenocytes (SPL) to support the response of MBP-stimulated IL-2 production. Hence, this subset provides a means to study regulation of THYB-2 specific co-stimulatory signals during the course of EAE. This study revealed that sensitization of Lewis rats with MBP in complete Freund's adjuvant induced a radioresistant subpopulation of co-stimulatory SPL that emerged during the remission phase of EAE. These radioresistant SPL provided specific accessory cell activities that fulfilled the co-stimulatory requirements of THYB-2 hybrids. These findings support the hypothesis that in vivo activation events elicit radioresistance in an emergent clonally expanding population of antigen-specific lymphocytes. A central prediction of this hypothesis is that cellular activation should confer radioresistance to co-stimulatory lymphocytes. This prediction was verified by the observation that in vitro activation of naive SPL with different B- and T-cell mitogens conferred radioresistance to co-stimulatory SPL. Mitogenic activation not only induced radioresistance but also dramatically augmented co-stimulatory activity of purified B cells. In summary, the results of this study support the hypothesis that in vivo activation of co-stimulatory lymphocytes may regulate activities of encephalitogenic T-helper cells during progression and remission of EAE.
用针对髓鞘碱性蛋白（MBP）的T细胞杂交瘤来评估Lewis大鼠实验性自身免疫性脑脊髓炎（EAE）缓解期共刺激信号的调节。T细胞杂交瘤的THYB - 1和THYB - 2亚群都识别MBP 72 - 86致脑炎区域中II类主要组织相容性复合体限制的决定簇。然而，THYB - 2杂交瘤独特地表达了对来自放射敏感脾细胞（SPL）的共刺激信号的额外需求，以支持MBP刺激的IL - 2产生反应。因此，该亚群提供了一种研究EAE过程中THYB - 2特异性共刺激信号调节的方法。本研究表明，用完全弗氏佐剂中的MBP致敏Lewis大鼠可诱导出在EAE缓解期出现的放射抗性共刺激SPL亚群。这些放射抗性SPL提供了满足THYB - 2杂交瘤共刺激需求的特异性辅助细胞活性。这些发现支持了这样一种假说，即体内激活事件会在新出现的克隆性扩增的抗原特异性淋巴细胞群体中引发放射抗性。该假说的一个核心预测是细胞激活应赋予共刺激淋巴细胞放射抗性。这一预测通过观察到用不同的B细胞和T细胞丝裂原体外激活幼稚SPL可赋予共刺激SPL放射抗性得到了验证。有丝分裂激活不仅诱导了放射抗性，还显著增强了纯化B细胞的共刺激活性。总之，本研究结果支持了这样一种假说，即在EAE的进展和缓解过程中，共刺激淋巴细胞的体内激活可能调节致脑炎辅助性T细胞的活性。
