Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 4
pubmed:dateCreated
2006-3-17
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).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1460-2156
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
129
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
986-95
pubmed:dateRevised
2006-11-15
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
pubmed:year
2006
pubmed:articleTitle
Shared blood and muscle CD8+ T-cell expansions in inclusion body myositis.
pubmed:affiliation
Service de médecine interne 1, Hôpital Pitié-Salpêtrière, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't