β cell-specific CD4+ T cell clonotypes in peripheral blood and the pancreatic islets are distinct

Li Li, Qiuming He, Alaina Garland, Zuoan Yi, Lydia T. Aybar, Thomas B. Kepler, Jeffrey A. Frelinger, Bo Wang, Roland Tisch

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Type 1 diabetes is an autoimmune disease mediated by β cell-specific CD4+ and CD8+ T cells. Tracking β cell-specific T cells is one approach to monitor the diabetogenic response in at risk or diabetic individuals. Such analyses, however, are limited to PBL because T cells infiltrating the pancreatic islets are normally inaccessible. A key issue is whether peripheral β cell-specific T cells accurately reflect those cells infiltrating the target tissue. We investigated the properties of CD4 + T cells specific for a mimetic epitope recognized by the BDC2.5 clonotypic TCR in NOD mice. Soluble IAg7-Ig (sIAg7-Ig) multimer complexes covalently linked to a mimetic BDC peptide (sIA g7-mBDC) were used to identify or isolate CD4+ T cells from PBL and the islets of NOD mice. A temporal increase in sIA g7-mBDC binding (g7-mBDC+) T cells corresponding with the progression of β cell autoimmunity was detected in both PBL and islets in NOD female mice. In contrast to T cells in PBL, however, the majority of islet g7-mBDC+ T cells exhibited a type 1 phenotype, and mediated diabetes upon transfer into NOD.scid recipients. TCR-β and CDR-β gene usage of single islet-infiltrating g7-mBDC+ CD4+ T cells from individual NOD mice showed a restricted repertoire dominated by one or two clones typically expressing TCR β-chain variable TRBV-15. In contrast, a distinct and diverse TCR repertoire was detected for PBL-derived g7-mBDC + T cells. These results demonstrate that PBL and islet CD4 + T cells specific for a given β cell epitope can differ regarding pathogenicity and TCR repertoire.

Original languageEnglish (US)
Pages (from-to)7585-7591
Number of pages7
JournalJournal of Immunology
Volume183
Issue number11
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Li, L., He, Q., Garland, A., Yi, Z., Aybar, L. T., Kepler, T. B., Frelinger, J. A., Wang, B., & Tisch, R. (2009). β cell-specific CD4+ T cell clonotypes in peripheral blood and the pancreatic islets are distinct. Journal of Immunology, 183(11), 7585-7591. https://doi.org/10.4049/jimmunol.0901587