文章基本信息

标题：The role of CD8+CD28− regulatory cells in suppressing myasthenia gravis-associated responses by a dual altered peptide ligand
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作者：Hava Ben-David ; Amir Sharabi ; Molly Dayan 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2007
卷号：104
期号：44
页码：17459-17464
DOI：10.1073/pnas.0708577104
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Myasthenia gravis (MG) and experimental autoimmune MG are T cell-dependent antibody-mediated autoimmune diseases. A dual altered peptide ligand (APL), composed of the tandemly arranged two single amino acid analogs of two myasthenogenic peptides, p195-212 and p259-271, down-regulated in vitro and in vivo MG-associated T cell responses. In the present study, we investigated the role of CD8+CD28- regulatory cells in the mechanism of action of the dual APL. We demonstrated that treatment of mice with the dual APL concomitant with immunization with a myasthenogenic peptide resulted in an increased population of CD8+CD28- cells that express forkhead box P3 (Foxp3). The dual APL inhibited the proliferation of lymph node (LN) cells of the Torpedo acetylcholine receptor-immunized WT C57BL/6 mice, whereas the inhibition was abrogated in CD8-/- knockout mice. Moreover, the dual APL did not inhibit the secretion of IFN-{gamma} by LN cells from CD8-/- mice immunized with Torpedo acetylcholine receptor. However, the mRNA expression of IL-10 and TGF-[beta] by LN cells from CD8-/- mice was up-regulated similarly to that of the WT mice. Furthermore, the dual APL elevated the proapoptotic markers caspases 3 and caspase 8, whereas it down-regulated the antiapoptotic marker Bcl-xL in both CD8-/- and WT mice. Finally, the dual APL-induced CD4+CD25+Foxp3+ cells were up-regulated in CD8-/- mice to a similar extent to that observed in the WT mice. Thus, we suggest that CD8+CD28- regulatory cells play a partial role in the mechanism of action by which the dual APL suppresses experimental autoimmune MG-associated T cell responses.
关键词：apoptotic markers ; cytokines ; regulatory T cells ; experimental autoimmune myasthenia gravis