Abstract：
:Autoimmunity is fundamentally a continuously evolving process. The autoimmune responses shift, drift and diversify with time not only to other epitopes in the original antigen but also to other related and sometimes to unrelated antigens. We have described a form of immune diversification--reciprocal T-B epitope spreading--where the activation of first T cells by epitopes from an autoantibody molecule could lead to help provided to a variety of B cells displaying a cross-reactive version of the original epitope. The response spreads in this way until large cohorts of T and B cells have expanded in lupus-prone mice. Such reciprocal T-B cell response can also be induced in normal animals, its extent is limited by the emergence of inhibitory T cells. The induction of such inhibitory T cells is generally impaired in lupus mice. The delivery of T cell epitopes via plasmid DNA vectors, however, can overcome this impairment in lupus mice. The inhibitory T cells thus induced can suppress autoantibody production and lupus disease by ablating or inhibiting autoreactive B cells. Thus, T-B diversification that develops spontaneously in lupus mice could be curtailed in normal animals by inhibitory T cells that emerge whenever there is an impending 'danger' of pathologic autoimmunity. We have successfully exploited this regulatory potential of the normal immune response to inhibit clinical autoimmunity. Understanding the mechanisms of autoimmune diversification in lupus mice and of its down-regulation in normal animals may pave the way for developing novel treatments for autoantibody-mediated diseases such as lupus.
journal_name
Mol Immunoljournal_title
Molecular immunologyauthors
Singh RRdoi
10.1016/j.molimm.2003.11.029subject
Has Abstractpub_date
2004-02-01 00:00:00pages
1137-45issue
14-15eissn
0161-5890issn
1872-9142pii
S0161589003003511journal_volume
40pub_type
杂志文章,评审abstract：BACKGROUND:A T cell subtype with the CD4+CD25-FoxP3+ phenotype was recently described. We aimed to investigate the frequency of these cells and their ability to produce cytokines in tumor-draining lymph nodes from patients with breast cancer (BC). MATERIALS AND METHODS:Mononuclear cells from lymph nodes of 20 patients...
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journal_title：Molecular immunology
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更新日期：2011-06-01 00:00:00
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更新日期：2019-03-01 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：1991-01-01 00:00:00
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pub_type： 杂志文章
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更新日期：2019-08-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/0161-5890(85)90180-4
更新日期：1985-05-01 00:00:00
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pub_type： 杂志文章
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更新日期：1990-01-01 00:00:00
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pub_type： 杂志文章
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更新日期：1982-02-01 00:00:00
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pub_type： 杂志文章
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doi：10.1016/0161-5890(95)00055-j
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pub_type： 杂志文章
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更新日期：1993-02-01 00:00:00
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pub_type： 杂志文章
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更新日期：1993-08-01 00:00:00
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pub_type： 杂志文章
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更新日期：2015-08-01 00:00:00
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journal_title：Molecular immunology
pub_type： 杂志文章
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更新日期：1988-04-01 00:00:00
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pub_type： 杂志文章
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更新日期：2004-07-01 00:00:00
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pub_type： 杂志文章
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更新日期：1986-04-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2000-01-01 00:00:00
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journal_title：Molecular immunology
pub_type： 杂志文章
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更新日期：1986-07-01 00:00:00
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journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2004.12.011
更新日期：2005-07-01 00:00:00
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journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(95)00030-i
更新日期：1995-06-01 00:00:00
