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 Citations (Scopus)

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

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Inbred NOD Mouse
T-Lymphocytes
Glucose-6-Phosphatase
Poisons
Type 1 Diabetes Mellitus
Sequence Analysis
Catalytic Domain
Proteins
Phosphotransferases
Peptides

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Vincent, B. G., Young, E. F., Buntzman, A. S., Stevens, R., Kepler, T. B., Tisch, R. M., ... Hess, P. R. (2010). Toxin-coupled MHC class I tetramers can specifically ablate autoreactive CD8+ T cells and delay diabetes in nonobese diabetic mice. Journal of Immunology, 184(8), 4196-4204. https://doi.org/10.4049/jimmunol.0903931

Toxin-coupled MHC class I tetramers can specifically ablate autoreactive CD8+ T cells and delay diabetes in nonobese diabetic mice. / Vincent, Benjamin G.; Young, Ellen F.; Buntzman, Adam S.; Stevens, Rosemary; Kepler, Thomas B.; Tisch, Roland M.; Frelinger, Jeffrey A; Hess, Paul R.

In: Journal of Immunology, Vol. 184, No. 8, 15.04.2010, p. 4196-4204.

Research output: Contribution to journalArticle

Vincent, Benjamin G. ; Young, Ellen F. ; Buntzman, Adam S. ; Stevens, Rosemary ; Kepler, Thomas B. ; Tisch, Roland M. ; Frelinger, Jeffrey A ; Hess, Paul R. / Toxin-coupled MHC class I tetramers can specifically ablate autoreactive CD8+ T cells and delay diabetes in nonobese diabetic mice. In: Journal of Immunology. 2010 ; Vol. 184, No. 8. pp. 4196-4204.
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