Triggering a second T cell receptor on diabetogenic T cells can prevent induction of diabetes

被引:20
作者
Fossati, G
Cooke, A
Papafio, RQ
Haskins, K
Stockinger, B
机构
[1] Natl Inst Med Res, Div Mol Immunol, London NW7 1AA, England
[2] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England
[3] Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA
基金
英国惠康基金;
关键词
diabetes; T cell receptor; anergy; T lymphocytes; islets;
D O I
10.1084/jem.190.4.577
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 X 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 Fl 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.
引用
收藏
页码:577 / 583
页数:7
相关论文
共 44 条
  • [1] ALAM SM, 1995, IMMUNITY, V3, P449
  • [2] Alam SM, 1998, J IMMUNOL, V160, P3883
  • [3] Dendritic cells acquire antigen from apoptotic cells and induce class I restricted CTLs
    Albert, ML
    Sauter, B
    Bhardwaj, N
    [J]. NATURE, 1998, 392 (6671) : 86 - 89
  • [4] ISLET-SPECIFIC T-CELL CLONES FROM THE NOD MOUSE RESPOND TO BETA-GRANULE ANTIGEN
    BERGMAN, B
    HASKINS, K
    [J]. DIABETES, 1994, 43 (02) : 197 - 203
  • [5] Dual T cell receptor T cells have a decreased sensitivity to physiological ligands due to reduced density of each T cell receptor
    Blichfeldt, E
    Munthe, LA
    Rotnes, JS
    Bogen, B
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (12) : 2876 - 2884
  • [6] EXCLUSION AND INCLUSION OF ALPHA-T-CELL AND BETA-T-CELL RECEPTOR ALLELES
    BORGULYA, P
    KISHI, H
    UEMATSU, Y
    VONBOEHMER, H
    [J]. CELL, 1992, 69 (03) : 529 - 537
  • [7] Interleukin 10 secretion and impaired effector function of major histocompatibility complex class II-restricted T cells anergized in vivo
    Buer, J
    Lanoue, A
    Franzke, A
    Garcia, C
    von Boehmer, H
    Sarukhan, A
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (02) : 177 - 183
  • [8] Mechanisms of peripheral tolerance and suppression induced by monoclonal antibodies to CD4 and CD8
    Cobbold, SP
    Adams, E
    Marshall, SE
    Davies, JD
    Waldmann, H
    [J]. IMMUNOLOGICAL REVIEWS, 1996, 149 : 5 - 33
  • [9] LIMITED CAPACITY FOR TOLERIZATION OF CD4(+) T-CELLS SPECIFIC FOR A PANCREATIC BETA-CELL NEO-ANTIGEN
    FORSTER, I
    HIROSE, R
    ARBEIT, JM
    CLAUSEN, BE
    HANAHAN, D
    [J]. IMMUNITY, 1995, 2 (06) : 573 - 585
  • [10] The avidity spectrum of T cell receptor interactions accounts for T cell anergy in a double transgenic model
    Girgis, L
    Davis, MM
    Fazekas de St Groth, B
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (02) : 265 - 277