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Identical Cell-Specific CD8⁺ T Cell Clonotypes Typically Reside in Both Peripheral Blood Lymphocyte and Pancreatic Islets¹

Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

A major issue regarding T cell responses in autoimmunity is how the repertoire compares between the periphery and target organ. In type 1 diabetes, the status of at-risk or diabetic individuals can be monitored by measuring cell-specific T cells isolated from PBL, but whether these T cells accurately reflect the repertoire residing in the pancreatic islets is unclear. The TCR repertoire of disease-relevant, tetramer-sorted CD8⁺ T cells was examined at the single-cell level in PBL, pancreatic lymph nodes (PLN), and the islets of individual NOD mice. CDR3 and CDR3 sequences demonstrated that the same repertoire of T cells in PBL was detected in the islets and PLN, although the frequency of specific clonotypes varied. Albeit infrequent, clonotypes that were prevalent in the islets but not found in PBL were also detected. cell Ag immunization expanded immunodominant PBL clonotypes present in the islets and PLN. These results show that insight into repertoire profiles of islet-infiltrating T cells can be obtained from PBL.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants R01AI058014 and R01AI52435, and Juvenile Diabetes Research Foundation Grant 1-2003-611. C.P.W. was supported by a Juvenile Diabetes Research Foundation postdoctoral fellowship. K.S.G. was supported by a National Institutes of Health training grant.

² Address correspondence and reprint requests to Dr. Roland Tisch, Department of Microbiology and Immunology, Mary Ellen Jones Building, Room 804, Campus Box 7290, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7290. E-mail address: rmtisch{at}med.unc.edu

³ Abbreviations used in this paper: T1D, type 1 diabetes; IGRP, islet specific glucose-6-phosphatase catalytic subunit-related protein; PLN, pancreatic lymph node; VRP, Venezuelan equine encephalitis virus replicon particle; HA, hemagglutinin; CD, celiac disease.

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