Abstract：
:Therapeutic efficacy of depleting B cells or blocking T-cell costimulation in rheumatoid arthritis (RA) has confirmed the critical pathogenic role of adaptive immune responses. Yet, RA preferentially affects elderly individuals, in whom adaptive immunity to exogenous antigens begins to fail. Here, we propose that senescence of the immune system is a risk factor for RA, with chronic inflammation resulting from the accumulation of degenerate T cells that have a low threshold for activation and utilize a spectrum of novel receptors to respond to microenvironmental cues. The process of immunosenescence is accelerated in RA and precedes the onset of disease, the acceleration, in part, being conferred by the HLA-DR4 haplotype. Naive CD4(+) T cells in RA are contracted in diversity and restricted in clonal burst. Senescence of effector CD4(+) T cells is associated with the loss of CD28 and the de novo expression of KIR2DS2, NKG2D, and CX(3)CR1, all of which function as costimulatory molecules and reduce the threshold for T-cell activation. The synovial microenvironment promotes chronic persistent immune responses by facilitating ectopic lymphoid neogenesis, such as the formation of aberrant germinal centers. With the propensity to develop complex lymphoid architectures and to provide optimal activation conditions for senescent CD4(+) T cells, the synovium becomes a natural target for pathogenic immune responses in prematurely aged individuals.
journal_name
Immunol Revjournal_title
Immunological reviewsauthors
Goronzy JJ,Weyand CMdoi
10.1111/j.0105-2896.2005.00245.xkeywords:
subject
Has Abstractpub_date
2005-04-01 00:00:00pages
55-73eissn
0105-2896issn
1600-065Xpii
IMR245journal_volume
204pub_type
杂志文章,评审abstract：:Chemokines control selective targeting of circulating leukocytes to the microvasculature by triggering inside-out signal transduction pathways leading to integrin-dependent adhesion. Integrin activation by chemokines is very rapid, is downmodulated within minutes and appears to involve both enhanced heterodimer latera...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2002.18604.x
更新日期：2002-08-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2006.00466.x
更新日期：2006-12-01 00:00:00
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doi：10.1111/j.1600-065X.2007.00564.x
更新日期：2007-12-01 00:00:00
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pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2011.01035.x
更新日期：2011-07-01 00:00:00
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pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2011.01045.x
更新日期：2011-09-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12366
更新日期：2015-11-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1984.tb01105.x
更新日期：1984-10-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
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更新日期：1999-02-01 00:00:00
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journal_title：Immunological reviews
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更新日期：1998-08-01 00:00:00
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journal_title：Immunological reviews
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更新日期：1997-02-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12267
更新日期：2015-03-01 00:00:00
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journal_title：Immunological reviews
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更新日期：2020-03-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
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更新日期：2000-04-01 00:00:00
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journal_title：Immunological reviews
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更新日期：2017-07-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章
doi：10.1111/j.1600-065x.1986.tb01167.x
更新日期：1986-12-01 00:00:00
abstract：SUMMARY:African trypanosomes are pathogens for humans and livestock. They are single-cell, extra-cellular parasites that cause persistent infections of the blood and induce profound immunosuppression. Here, we review recent work on experimental African trypanosomiasis, especially infections with Trypanosoma congolense,...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2008.00675.x
更新日期：2008-10-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2000.17720.x
更新日期：2000-10-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12374
更新日期：2016-01-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2001.790108.x
更新日期：2001-02-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
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更新日期：1999-06-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
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更新日期：1999-12-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
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更新日期：2001-06-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
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更新日期：2008-06-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2003.00028.x
更新日期：2003-04-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1990.tb00572.x
更新日期：1990-10-01 00:00:00
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journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2006.00412.x
更新日期：2006-08-01 00:00:00
abstract：:The molecular analysis of the Class II region of the MHC of mice and of humans has to date led to some important conclusions. These regions encode sizeable families of related loci, at least 2 alpha and 6 beta in mice and 6 alpha and 7 beta in man. In addition to the sizeable number of potential molecules that could b...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1985.tb01125.x
更新日期：1985-07-01 00:00:00
abstract：:Superantigens (SAGs) are a class of disease-causing and immunostimulatory proteins of bacterial or viral origin that activate T cells by binding to the V beta domain of the T-cell antigen receptor (TCR). The three-dimensional structure of the complex between a TCR beta chain (mouse V beta 8.2-J beta 2.1-C beta 1) and ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01196.x
更新日期：1998-06-01 00:00:00
abstract：:Inflammasomes are the central signaling hubs of the inflammatory response. They process cytosolic evidence of infection, cell damage, or metabolic disturbances, and elicit a pro-inflammatory response mediated by members of the interleukin-1 family of cytokines and pyroptotoic cell death. On the molecular level, this i...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12611
更新日期：2018-01-01 00:00:00
abstract：:Adoptive transfer of TCR-transgenic T cells uniformly expressing an identifiable TCR of known peptide/MHC specificity can be used to monitor the in vivo behavior of antigen-specific T cells. We have used this system to show that naive T cells are initially activated within the T-cell zones of secondary lymphoid tissue...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1997.tb00959.x
更新日期：1997-04-01 00:00:00
