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
Publication statusPublished - Dec 1 2009
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Li, L., He, Q., Garland, A., Yi, Z., Aybar, L. T., Kepler, T. 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