Source:http://linkedlifedata.com/resource/pubmed/id/16455793
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
Pt 4
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pubmed:dateCreated |
2006-3-17
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pubmed:abstractText |
Inclusion body myositis (IBM) is the most frequent inflammatory myopathy over the age of fifty. Pathological findings suggest that two processes may contribute to IBM pathogenesis: a primary degenerative process affecting muscle fibre and/or an autoimmune process mediated by major histocompatibility complex (MHC) class-I-restricted cytotoxic CD8+ T cells. Previous studies have demonstrated that muscle-infiltrating CD8+ T cells in IBM display restricted expression of T-cell receptor (TCR)-BV families or evidenced oligoclonal T-cell expansions. This study was performed to investigate whether blood T cells similarly exhibit clonal expansions due to the recirculation of muscle-infiltrating T cells in the periphery. For this, we studied the T-cell repertoire of 17 IBM patients by complementarity-determining-region (CDR) 3 length distribution (immunoscope) analysis of TCR-B transcripts. Mean age was 68 years (range 53-88) and mean duration of the disease was 6.5 years (2-20). Oligoclonal T-cell expansions were observed in the blood of IBM patients. The quantitative average perturbation D index was significantly increased in IBM patients [D = 13.7% +/- 1.2%, mean +/- standard error of measurement (SEM)] as compared with 17 age-matched controls suffering from connective tissue diseases not associated with T-cell repertoire perturbation, that is, dermatomyositis (DM) and systemic sclerosis (9.3 +/- 0.6%, P < 0.005). Nevertheless, there was no correlation between the level of blood perturbation and muscle inflammation. Sorting experiments showed that these perturbations were due to oligoclonal expansions of CD8+ T cells. In the three IBM patients analysed, we could relate the blood expansions to T-cell clones also found in muscle. The clonally expanded blood T cells dramatically responded to interleukin-2 (IL-2) in vitro, suggesting that they had been primed in vivo, presumably in response to yet unknown muscle auto-antigens. Together, our results indicate that clonally expanded muscle-infiltrating CD8+ T cells re-circulate in the blood and support the concept of a CD8+ T-cell-mediated autoimmune component in IBM, similarly to what is observed in polymyositis (PM).
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1460-2156
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pubmed:author |
pubmed-author:AmouraZahirZ,
pubmed-author:BenvenisteOlivierO,
pubmed-author:BoyerOlivierO,
pubmed-author:DimitriDaliaD,
pubmed-author:DubourgOdileO,
pubmed-author:EymardBrunoB,
pubmed-author:HersonSergeS,
pubmed-author:JeanLaetitiaL,
pubmed-author:KlatzmannDavidD,
pubmed-author:MaisonobeThierryT,
pubmed-author:PietteJean-CharlesJC,
pubmed-author:TievKietK
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pubmed:issnType |
Electronic
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pubmed:volume |
129
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
986-95
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16455793-Aged,
pubmed-meshheading:16455793-Aged, 80 and over,
pubmed-meshheading:16455793-Autoimmune Diseases,
pubmed-meshheading:16455793-CD4-Positive T-Lymphocytes,
pubmed-meshheading:16455793-CD8-Positive T-Lymphocytes,
pubmed-meshheading:16455793-Cell Movement,
pubmed-meshheading:16455793-Cells, Cultured,
pubmed-meshheading:16455793-Complementarity Determining Regions,
pubmed-meshheading:16455793-Female,
pubmed-meshheading:16455793-Humans,
pubmed-meshheading:16455793-Interleukin-2,
pubmed-meshheading:16455793-Lymphocyte Activation,
pubmed-meshheading:16455793-Male,
pubmed-meshheading:16455793-Middle Aged,
pubmed-meshheading:16455793-Muscle, Skeletal,
pubmed-meshheading:16455793-Myositis, Inclusion Body,
pubmed-meshheading:16455793-Severity of Illness Index,
pubmed-meshheading:16455793-T-Lymphocyte Subsets
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pubmed:year |
2006
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pubmed:articleTitle |
Shared blood and muscle CD8+ T-cell expansions in inclusion body myositis.
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pubmed:affiliation |
Service de médecine interne 1, Hôpital Pitié-Salpêtrière, Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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