Deng C, Goluszko E, Christadoss P
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
J Immunol. 2001 Mar 1;166(5):3458-67. doi: 10.4049/jimmunol.166.5.3458.
The cellular mechanisms of high dose systemic acetylcholine receptor (AChR) T cell epitope, alpha 146--162 peptide-induced tolerance in experimental myasthenia gravis were examined. CD4 cells are the prime target for alpha 146--162 peptide-induced tolerance. The expression of CD69, Fas, and B7.2 molecules on AChR-immune lymphocytes was enhanced within 4--12 h after tolerance induction. A high dose of alpha 146--162 peptide in IFA failed to suppress T cell proliferation and/or clinical myasthenia gravis in lpr and gld mice deficient in Fas and Fas ligand, respectively. A high dose of alpha 146--162 peptide in IFA in AChR-immunized mice induced apoptosis of BV6 cells. Further, reconstitution of IL-2 in vitro-recovered alpha 146--162 peptide tolerized T cell proliferation, IFN-gamma, and IL-10 production. The findings implicate the possible role of Fas-/Fas ligand-mediated apoptosis and the resulting clonal anergy as the mechanisms of high dose AChR alpha 146--162 peptide-induced tolerance on CD4 cells.
研究了高剂量全身性乙酰胆碱受体（AChR）T细胞表位α146 - 162肽在实验性重症肌无力中诱导耐受的细胞机制。CD4细胞是α146 - 162肽诱导耐受的主要靶点。在诱导耐受后4 - 12小时内，AChR免疫淋巴细胞上CD69、Fas和B7.2分子的表达增强。分别缺乏Fas和Fas配体的lpr和gld小鼠中，IFA中的高剂量α146 - 162肽未能抑制T细胞增殖和/或临床重症肌无力。AChR免疫小鼠中IFA中的高剂量α146 - 162肽诱导BV6细胞凋亡。此外，体外恢复IL-2可使α146 - 162肽耐受的T细胞增殖、IFN-γ和IL-10产生。这些发现表明Fas - /Fas配体介导的凋亡以及由此产生的克隆无能可能是高剂量AChRα146 - 162肽诱导CD4细胞耐受的机制。
