Age-dependent T cell tolerance and autoimmunity to myelin basic protein

被引:80
作者
Huseby, ES
Sather, B
Huseby, PG
Goverman, J [1 ]
机构
[1] Univ Washington, Dept Immunol, Seattle, WA 98195 USA
[2] Univ Washington, Dept Mol Biotechnol, Seattle, WA 98195 USA
关键词
D O I
10.1016/S1074-7613(01)00127-3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, is induced by activating a subset of myelin basic protein (MBP)-specific T cells that have escaped tolerance induction. Here, we define the tolerance mechanisms that eliminate the majority of MBP-specific T cells from the periphery. We show that MBP-specific T cells undergo central tolerance mediated by bone marrow-derived antigen-presenting cells presenting exogenously derived MBP epitopes. The efficiency of tolerance is age dependent, reflecting the developmentally regulated expression of MBP. Dependence of tolerance on the amount of MBP expressed in vivo results in an age window of susceptibility to EAE in mice that peaks during puberty. These results suggest that facto rs regulating expression of self-antigens in vivo can influence susceptibility to autoimmunity.
引用
收藏
页码:471 / 481
页数:11
相关论文
共 44 条
  • [1] High frequency of autoreactive myelin proteolipid protein-specific T cells in the periphery of naive mice: Mechanisms of selection of the self-reactive repertoire
    Anderson, AC
    Nicholson, LB
    Legge, KL
    Turchin, V
    Zaghouani, H
    Kuchroo, VK
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (05) : 761 - 770
  • [2] Cellular interactions in thymocyte development
    Anderson, G
    Moore, NC
    Owen, JJT
    Jenkinson, EJ
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 : 73 - 99
  • [3] ACCUMULATION OF 4 MYELIN BASIC-PROTEINS IN MOUSE-BRAIN DURING DEVELOPMENT
    BARBARESE, E
    CARSON, JH
    BRAUN, PE
    [J]. JOURNAL OF NEUROCHEMISTRY, 1978, 31 (04) : 779 - 782
  • [4] RADIATION CHIMAERA, HOST H-2 ANTIGENS DETERMINE IMMUNE RESPONSIVENESS OF DONOR CYTOTOXIC CELLS
    BEVAN, MJ
    [J]. NATURE, 1977, 269 (5627) : 417 - 418
  • [5] CAMPAGNONI AT, 1993, J BIOL CHEM, V268, P4930
  • [6] CERVICAL LYMPHATICS, THE BLOOD-BRAIN-BARRIER AND THE IMMUNOREACTIVITY OF THE BRAIN - A NEW VIEW
    CSERR, HF
    KNOPF, PM
    [J]. IMMUNOLOGY TODAY, 1992, 13 (12): : 507 - 512
  • [7] IMMUNOCHEMICAL STUDIES OF MYELIN BASIC-PROTEIN IN SHIVERER MOUSE DEVOID OF MAJOR DENSE LINE OF MYELIN
    DUPOUEY, P
    JACQUE, C
    BOURRE, JM
    CESSELIN, F
    PRIVAT, A
    BAUMANN, N
    [J]. NEUROSCIENCE LETTERS, 1979, 12 (01) : 113 - 118
  • [8] THYMIC EXPRESSION OF THE GOLLI-MYELIN BASIC-PROTEIN GENE IN THE SJL/J MOUSE
    FRITZ, RB
    KALVAKOLANU, I
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 1995, 57 (1-2) : 93 - 99
  • [9] TRANSGENIC MICE THAT EXPRESS A MYELIN BASIC PROTEIN-SPECIFIC T-CELL RECEPTOR DEVELOP SPONTANEOUS AUTOIMMUNITY
    GOVERMAN, J
    WOODS, A
    LARSON, L
    WEINER, LP
    HOOD, L
    ZALLER, DM
    [J]. CELL, 1993, 72 (04) : 551 - 560
  • [10] Differential tolerance is induced in T cells recognizing distinct epitopes of myelin basic protein
    Harrington, CJ
    Paez, A
    Hunkapiller, T
    Mannikko, V
    Brabb, T
    Ahearn, ME
    Beeson, C
    Goverman, J
    [J]. IMMUNITY, 1998, 8 (05) : 571 - 580