Linked Life Data

16461801

Source:http://linkedlifedata.com/resource/pubmed/id/16461801

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2006-2-7
pubmed:abstractText
The pathogenesis of rheumatoid arthritis (RA) is determined by a complex interaction of genetic and environmental factors. Of all risk factors, age has the largest impact. RA occurs most often during the postmenopausal period of life, with incidence rates peaking in the eighth decade. While age is generally accepted as an etiologic factor for failure of immunocompetence, much less is understood about the role of T-cell senescence in autoimmunity. We have hypothesized that senescent T cells are particularly prone to be activated in specialized microenvironments, such as the synovial membrane. CD4 T cells in the senescence program were identified by the loss of CD28. Gene expression profiling documented that CD28- T cells have acquired a spectrum of regulatory receptors that are usually seen only on NK cells. Such regulatory receptors include stimulatory and inhibitory members of the killer immunoglobulin-like receptor (KIR) family, the stimulatory c-type lectin receptor NKG2D, and CX3CR1, the receptor for the chemokine fractalkine. Synovial fibroblasts express the relevant ligands, thus providing stimulatory signals to tissue-infiltrating T cells. The signaling pathways of these regulatory receptors are complex and dependent on the individual T cells, some of which express important adapter molecules such as DAP10 and DAP12. Inhibitory KIRs on T cells are often only partially functional. Our data suggest that, by virtue of altered receptor profiles, conventional tolerance mechanisms can be evaded in the aging host. By acquiring a new set of regulatory receptors, senescent CD4 T cells become responsive to novel environmental cues and find ideal stimulatory conditions in the synovial microenvironment.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:volume
1062
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
182-94
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Costimulatory pathways in rheumatoid synovitis and T-cell senescence.
pubmed:affiliation
Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory University School of Medicine, Rm. 1003, Woodruff Memorial Research Bldg., 101 Woodruff Circle, Atlanta, GA 30322, USA. jgoronz@emory.edu
pubmed:publicationType
Journal Article, Review, Research Support, N.I.H., Extramural