Disruption of T cell tolerance to self-immunoglobulin causes polyclonal B cell stimulation followed by inactivation of responding autoreactive T cells

被引:7
作者
Choudhury, A [1 ]
Mukherjee, P [1 ]
Basu, SK [1 ]
George, A [1 ]
Rath, S [1 ]
Bal, V [1 ]
机构
[1] Natl Inst Immunol, New Delhi 110067, India
关键词
D O I
10.4049/jimmunol.164.4.1713
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Scavenger receptor (SR)-specific delivery by maleylation of a ubiquitous self-protein, Ig, to SR-bearing APCs results in self-limiting induction of autoimmune effects in vivo. Immunization with maleyl-Ig breaks T cell tolerance to self-Ig and causes hypergammaglobulinemia, with increases in spleen weight and cellularity. The majority of splenic B cells show an activated phenotype upon maleyl-Ig immunization, leading to large-scale conversion to a CD138(+) phenotype and to significant increases in CD138-expressing splenic plasma cells. The polyclonal B cell activation, hypergammaglobulinemia, and autoreactive Ig-specific T cell responses decline over a 2-mo period postimmunization. Following adoptive transfer, T cells from maleyl-Ig-immune mice taken at 2 wk postimmunization can induce hypergammaglobulinemia in the recipients, but those taken at 10 wk postimmunization cannot. Hypergammaglobulinemia in the adoptive transfer recipients is also transient and is followed by an inability to respond to fresh maleyl-Ig immunization, suggesting that the autoreactive Ig-specific T cells are inactivated peripherally following disruption of tolerance. Thus, although autoreactive T cell responses to a ubiquitous self-Ag, Ig, are induced by SR-mediated delivery to professional APCs in vivo resulting in autoimmune pathophysiological effects, they are effectively and rapidly turned off by inactivation of these activated Ig-specific T cells in vivo.
引用
收藏
页码:1713 / 1721
页数:9
相关论文
共 54 条
  • [1] Functional diversity of helper T lymphocytes
    Abbas, AK
    Murphy, KM
    Sher, A
    [J]. NATURE, 1996, 383 (6603) : 787 - 793
  • [2] Abraham R, 1997, J IMMUNOL, V158, P4029
  • [3] ABRAHAM R, 1995, J IMMUNOL, V154, P1
  • [4] AGE-ASSOCIATED CHANGES IN THE B-CELL REPERTOIRE - EFFECT OF AGE ON RAG-1 GENE-EXPRESSION IN MURINE BONE-MARROW
    BENYEHUDA, A
    SZABO, P
    WEKSLER, ME
    [J]. IMMUNOLOGY LETTERS, 1994, 40 (03) : 287 - 289
  • [5] TOLERANCE IN TRANSGENIC MICE EXPRESSING MAJOR HISTOCOMPATIBILITY MOLECULES EXTRATHYMICALLY ON PANCREATIC-CELLS
    BURKLY, LC
    LO, D
    FLAVELL, RA
    [J]. SCIENCE, 1990, 248 (4961) : 1364 - 1368
  • [6] SELECTIVE DELIVERY OF DRUGS TO MACROPHAGES THROUGH A HIGHLY SPECIFIC RECEPTOR - AN EFFICIENT CHEMOTHERAPEUTIC APPROACH AGAINST LEISHMANIASIS
    CHAUDHURI, G
    MUKHOPADHYAY, A
    BASU, SK
    [J]. BIOCHEMICAL PHARMACOLOGY, 1989, 38 (18) : 2995 - 3002
  • [7] SPECIFICITY AND PROMISCUITY AMONG NATURALLY PROCESSED PEPTIDES BOUND TO HLA-DR ALLELES
    CHICZ, RM
    URBAN, RG
    GORGA, JC
    VIGNALI, DAA
    LANE, WS
    STROMINGER, JL
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (01) : 27 - 47
  • [8] Infectious tolerance
    Cobbold, S
    Waldmann, H
    [J]. CURRENT OPINION IN IMMUNOLOGY, 1998, 10 (05) : 518 - 524
  • [9] Natural autoantibodies
    Coutinho, A
    Kazatchkine, MD
    Avrameas, S
    [J]. CURRENT OPINION IN IMMUNOLOGY, 1995, 7 (06) : 812 - 818
  • [10] Accessory molecule and costimulation requirements for CD4 T cell response
    Croft, M
    Dubey, C
    [J]. CRITICAL REVIEWS IN IMMUNOLOGY, 1997, 17 (01) : 89 - 118