Toxin-coupled MHC class I tetramers can specifically ablate autoreactive CD8+ T cells and delay diabetes in nonobese diabetic mice.

Toxin-coupled MHC class I tetramers can specifically ablate autoreactive CD8+ T cells and delay diabetes in nonobese diabetic mice.
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DOI:
10.4049/jimmunol.0903931
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发表时间:
2010-04-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Hess PR
Hess PR
中科院分区:
其他
文献类型:
--
作者:
Vincent BG;Young EF;Buntzman AS;Stevens R;Kepler TB;Tisch RM;Frelinger JA;Hess PR

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There is compelling evidence that self reactive CD8+ T cells are a major factor in development and progression of Type 1 diabetes in animals and humans. Hence, great effort has been expended to define the specificity of autoimmune CD8+ T cells, and to alter their responses. Much work has focused on tolerization of T cells using proteins or peptides. A weakness in this approach is residual autoreactive T cells may be activated and exacerbate disease. In this report we use a novel approach - toxin coupled MHC class I tetramers. Used for some time to identify antigen specific cells, here we use that same property to delete the antigen specific cells. We show saporin coupled tetramers can delete IGRP reactive T cells in vitro and in vivo. Sequence analysis of TCRβ chains of IGRP+ cells reveals the repertoire complexity in the islets is markedly decreased as NOD mice age and significantly altered in toxic tetramer treated NOD mice. Further tetramer+ T cells in the islets are almost completely deleted and surprisingly loss of tetramer+ T cells in the islets is long lasting. Finally, we show deletion at 8 weeks of age of IGRP+ CD8+ T cells, but not DMK or InsB reactive cells, significantly delays diabetes in NOD mice.
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