In this paper, we test the hypothesis that triggering of a second T cell receptor (TCR) expressed on diabetogenic T cells might initiate the onset of diabetes. A cross between two TCR-transgenic strains, the BDC2.5 strain that carries diabetogenic TCRs and the A18 strain that carries receptors specific for C5, was set up to monitor development of diabetes after activation through the C5 TCR. F1 BDC2.5 × A18 mice developed diabetes spontaneously beyond 3–4 mo of age. Although their T cells express both TCRs constitutively, the A18 receptor is expressed at extremely low levels. In vitro activation of dual TCR T cells followed by adoptive transfer into neonatal or adult F1 mice resulted in diabetes onset and death within 10 d after transfer. In contrast, in vivo immunization of F1 mice with different forms of C5 antigen not only failed to induce diabetes but protected mice from the spontaneous onset of diabetes. We propose that antigenic stimulation of cells with low levels of TCR produces signals inadequate for full activation, resulting instead in anergy.
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16 August 1999
Article|
August 16 1999
Triggering a Second T Cell Receptor on Diabetogenic T Cells Can Prevent Induction of Diabetes
Gianluca Fossati,
Gianluca Fossati
aFrom the Division of Molecular Immunology, The National Institute for Medical Research, London NW7 1AA, United Kingdom
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Anne Cooke,
Anne Cooke
bDepartment of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom
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Ruby Quartey Papafio,
Ruby Quartey Papafio
bDepartment of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom
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Kathryn Haskins,
Kathryn Haskins
cDepartment of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80262
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Brigitta Stockinger
Brigitta Stockinger
aFrom the Division of Molecular Immunology, The National Institute for Medical Research, London NW7 1AA, United Kingdom
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Gianluca Fossati
aFrom the Division of Molecular Immunology, The National Institute for Medical Research, London NW7 1AA, United Kingdom
Anne Cooke
bDepartment of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom
Ruby Quartey Papafio
bDepartment of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom
Kathryn Haskins
cDepartment of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80262
Brigitta Stockinger
aFrom the Division of Molecular Immunology, The National Institute for Medical Research, London NW7 1AA, United Kingdom
Received:
February 24 1999
Revision Requested:
June 14 1999
Accepted:
June 17 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 1999 The Rockefeller University Press
1999
The Rockefeller University Press
J Exp Med (1999) 190 (4): 577–584.
Article history
Received:
February 24 1999
Revision Requested:
June 14 1999
Accepted:
June 17 1999
Citation
Gianluca Fossati, Anne Cooke, Ruby Quartey Papafio, Kathryn Haskins, Brigitta Stockinger; Triggering a Second T Cell Receptor on Diabetogenic T Cells Can Prevent Induction of Diabetes. J Exp Med 16 August 1999; 190 (4): 577–584. doi: https://doi.org/10.1084/jem.190.4.577
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