Fallis R J, McFarlin D E
Neuroimmunology Branch, NINDS, Bethesda, MD 20892.
J Immunol. 1989 Oct 1;143(7):2160-5.
We have examined the possibility that Ag-specific CTL responses may play a role in the pathogenesis of CREAE by using an effector T cell line (LN400) specifically reactive to the SJL encephalitogenic epitope defined by myelin basic protein MBP residues(90-101). The LN400 cell line was capable of adoptively transferring CREAE to naive SJL mice and proliferated specifically to synthetic peptides corresponding to MBP residues(90-101) and an N-acetylated analogue of this epitope, as well as MBP. Moreover, the cell line generated Ag-specific CTL responses only against syngeneic targets that had been pulsed with these Ag. Targets pulsed with irrelevant Ag were not lysed. These CTL responses were MHC restricted to H-2s and were inhibited if targets were preincubated with mAb specific for relevant class II Ag. No inhibition was seen if targets were preincubated with mAb specific for class I Ag, indicating that the CTL responses generated by this L3T4+ Lyt-2.2- cell lines were class II restricted. Studies designed to detect nonspecific CTL through a bystander mechanism failed to demonstrate significant lysis of bystander targets by this Ag-specific cell line. These findings have relevance in defining potential mechanisms of disease induction in this model autoimmune disease.
我们通过使用对由髓鞘碱性蛋白(MBP)残基(90 - 101)所定义的SJL致脑炎表位具有特异性反应的效应T细胞系(LN400),研究了抗原特异性CTL反应可能在实验性自身免疫性脑脊髓炎(CREAE)发病机制中发挥作用的可能性。LN400细胞系能够将CREAE过继转移给未致敏的SJL小鼠,并能特异性增殖以响应与MBP残基(90 - 101)相对应的合成肽、该表位的N - 乙酰化类似物以及MBP。此外,该细胞系仅对用这些抗原脉冲处理过的同基因靶标产生抗原特异性CTL反应。用无关抗原脉冲处理的靶标未被裂解。这些CTL反应受MHC限制于H - 2s,并且如果靶标预先与针对相关II类抗原的单克隆抗体一起孵育,反应会受到抑制。如果靶标预先与针对I类抗原的单克隆抗体一起孵育,则未见抑制,这表明由该L3T4 + Lyt - 2.2 - 细胞系产生的CTL反应受II类限制。旨在通过旁观者机制检测非特异性CTL的研究未能证明该抗原特异性细胞系对旁观者靶标有明显的裂解作用。这些发现对于确定这种模型自身免疫性疾病中疾病诱导的潜在机制具有重要意义。