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

Benjamin G. Vincent, Ellen F. Young, Adam S. Buntzman, Rosemary Stevens, Thomas B. Kepler, Roland M. Tisch, Jeffrey A. Frelinger, Paul R. Hess

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

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 that 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 Ag-specific cells, in this study, we use that same property to delete the Ag-specific cells. We show that saporin-coupled tetramers can delete islet-specific glucose-6-phosphatase catalytic subunit-related protein (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 wk of age of IGRP+ CD8 + T cells, but not dystophia myotonica kinase- or insulin B-reactive cells, significantly delays diabetes in NOD mice.

Original languageEnglish (US)
Pages (from-to)4196-4204
Number of pages9
JournalJournal of Immunology
Volume184
Issue number8
DOIs
StatePublished - Apr 15 2010
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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