HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ejrnaes, M. Articles by von Herrath, M. Search for Related Content PubMed PubMed Citation Articles by Ejrnaes, M. Articles by von Herrath, M.

Different Diabetogenic Potential of Autoaggressive CD8⁺ Clones Associated with IFN--Inducible Protein 10 (CXC Chemokine Ligand 10) Production but Not Cytokine Expression, Cytolytic Activity, or Homing Characteristics¹

Mette Ejrnaes^*, Nicoline Videbaek, Urs Christen^*, Anne Cooke, Birgitte K. Michelsen and Matthias von Herrath^2,*

^* Department of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; Hagedorn Research Institute, Gentofte, Denmark; and Department of Pathology, University of Cambridge, Cambridge, United Kingdom

Type 1 diabetes mellitus is an autoimmune disease characterized by T cell-mediated destruction of the insulin-producing cells in the islets of Langerhans. From studies in animal models, CD8⁺ T cells recognizing autoantigens such as islet-specific glucose-6-phosphatase catalytic subunit-related protein, insulin, or glutamic acid decarboxylase (GAD) are believed to play important roles in both the early and late phases of cell destruction. In this study, we investigated the factors governing the diabetogenic potential of autoreactive CD8⁺ clones isolated from spleens of NOD mice that had been immunized with GAD65_515–524 or insulin B-chain_15–23 peptides. Although these two clones were identical in most phenotypic and functional aspects, for example cytokine production and killing of autologous cells, they differed in the expression of IFN--inducible protein-10, which was only produced at high levels by the insulin-specific clone, but not by the GAD65-specific clone, and other autoantigen-specific nonpathogenic CD8 T cell clones. Interestingly, upon i.p. injection into neonatal mice, only the insulin B-chain_15–23-reactive CD8⁺ T clone accelerated diabetes in all recipients after 4 wk, although both insulin- and GAD-reactive clones homed to pancreas and pancreatic lymph nodes with similar kinetics. Diabetes was associated with increased pancreatic T cell infiltration and, in particular, recruitment of macrophages. Thus, secretion of IFN--inducible protein-10 by autoaggressive CD8⁺ lymphocytes might determine their diabetogenic capacity by affecting recruitment of cells to the insulitic lesion.

This article has been cited by other articles:

				C. Papewalis, M. Wuttke, J. Seissler, Y. Meyer, C. Kessler, B. Jacobs, E. Ullrich, H. S. Willenberg, S. Schinner, T. Baehring, et al. Dendritic Cell Vaccination with Xenogenic Polypeptide Hormone Induces Tumor Rejection in Neuroendocrine Cancer Clin. Cancer Res., July 1, 2008; 14(13): 4298 - 4305. [Abstract] [Full Text] [PDF]

				M. M. Martinic, A. E. Juedes, D. Bresson, D. Homann, K. Skak, C. Huber, E. Ling, M. Ejrnaes, T. Wolfe, L. Togher, et al. Minimal Impact of a De Novo-Expressed {beta}-Cell Autoantigen on Spontaneous Diabetes Development in NOD Mice Diabetes, April 1, 2007; 56(4): 1059 - 1068. [Abstract] [Full Text] [PDF]

				T. Raine, P. Zaccone, P. Mastroeni, and A. Cooke Salmonella typhimurium Infection in Nonobese Diabetic Mice Generates Immunomodulatory Dendritic Cells Able to Prevent Type 1 Diabetes J. Immunol., August 15, 2006; 177(4): 2224 - 2233. [Abstract] [Full Text] [PDF]