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 Ramanathan, S. Articles by Poussier, P. Search for Related Content PubMed PubMed Citation Articles by Ramanathan, S. Articles by Poussier, P. Pubmed/NCBI databases Medline Plus Health Information Diabetes Type 1

T Cell Reconstitution of BB/W Rats After the Initiation of Insulitis Precipitates the Onset of Diabetes¹

Departments of Immunology and Medicine, University of Toronto, Toronto, Ontario, Canada

One of the diabetes susceptibility genes of the BB/W (Biobreeding/Worcester) rat maps to the lyp locus on chromosome 4. The BB/W lyp allele is responsible for a severe peripheral T lymphopenia. Correction of this lymphopenia by transfer of normal, histocompatible T cells prevents diabetes, providing T cell reconstitution is initiated before insulitis. We have analyzed this time-dependent regulation of the diabetogenic process by normal T cells. We demonstrate that T cell reconstitution after the initiation of insulitis precipitates the onset of diabetes through the recruitment of donor T cells to the autoimmune process. This inability of normal T cells to regulate primed diabetogenic BB/W T cells and their own autoreactive potential were observed when normal T cells outnumbered pathogenic T cells by approximately 1000-fold. Analysis of donor-derived T cells recovered from BB/W rats that were reconstituted before insulitis, and hence protected from diabetes, demonstrates that early T cell reconstitution of BB/W rats does not result in a long term physical or functional depletion of islet cell-specific T cell precursors among donor cells or in the expansion of T cells that can regulate the activation and expansion of diabetogenic T cells.

This article has been cited by other articles:

				D. Lundsgaard, T. L. Holm, L. Hornum, and H. Markholst In Vivo Control of Diabetogenic T-Cells by Regulatory CD4+CD25+ T-Cells Expressing Foxp3 Diabetes, April 1, 2005; 54(4): 1040 - 1047. [Abstract] [Full Text] [PDF]

				S. Ramanathan, M.-T. Bihoreau, A. D. Paterson, L. Marandi, D. Gauguier, and P. Poussier Thymectomy and Radiation-Induced Type 1 Diabetes in Nonlymphopenic BB Rats Diabetes, October 1, 2002; 51(10): 2975 - 2981. [Abstract] [Full Text] [PDF]

				S. Ramanathan, L. Marandi, and P. Poussier Evidence for the Extrathymic Origin of Intestinal TCR{gamma}{delta}+ T Cells in Normal Rats and for an Impairment of This Differentiation Pathway in BB Rats J. Immunol., March 1, 2002; 168(5): 2182 - 2187. [Abstract] [Full Text] [PDF]

				P. P.L. Chiu, D. V. Serreze, and J. S. Danska Development and Function of Diabetogenic T-cells in B-cell-Deficient Nonobese Diabetic Mice Diabetes, April 1, 2001; 50(4): 763 - 770. [Abstract] [Full Text]