β Cell-Specific CD4+ T Cell Clonotypes in Peripheral Blood and the Pancreatic Islets Are Distinct

  • Li L
  • He Q
  • Garland A
  • et al.
27Citations
Citations of this article
28Readers
Mendeley users who have this article in their library.

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 (sIAg7-mBDC) were used to identify or isolate CD4+ T cells from PBL and the islets of NOD mice. A temporal increase in sIAg7-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.

Cite

CITATION STYLE

APA

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. The Journal of Immunology, 183(11), 7585–7591. https://doi.org/10.4049/jimmunol.0901587

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free