Brain Advance Access originally published online on February 2, 2006
Brain 2006 129(4):986-995; doi:10.1093/brain/awl020
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Shared blood and muscle CD8+ T-cell expansions in inclusion body myositis
1 Service de médecine interne 1, 2 Laboratoire de neuropathologie, 3 Institut de myologie, 4 Service de médecine interne 2, Hôpital Pitié-Salpêtrière, 5 Service de médecine interne, Hôpital Saint-Antoine, 6 CNRS UMR 7087, Hôpital Pitié-Salpêtrière, Paris and 7 INSERM U 519, Equipe Avenir ‘Immuno-myologie fondamentale et biothérapies’, Rouen, France
Correspondence to: Olivier Benveniste, Service de médecine interne 1, Hôpital Pitié-Salpêtrière, 47 Bd de l'hôpital, 75013 Paris, France E-mail: olivier.benveniste{at}psl.ap-hop-paris.fr
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).
Key Words: inclusion body myositis; T-cell immunology; T-cell receptors
Abbreviations: CDR = complementarity-determining-region; DM = dermatomyositis; IBM = inclusion body myositis; IL-2 = interleukin-2; MHC = major histocompatibility complex; PBMC = peripheral blood mononuclear cells; PM = polymyositis; SEM = standard error of measurement; TCR = T-cell receptor
.
Received September 10, 2005. Revised December 12, 2005. Accepted January 5, 2006.
* These two authors contributed equally to this work
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Allenbach, S. Solly, S. Gregoire, O. Dubourg, B. Salomon, G. Butler-Browne, L. Musset, S. Herson, D. Klatzmann, and O. Benveniste Role of Regulatory T Cells in a New Mouse Model of Experimental Autoimmune Myositis Am. J. Pathol., March 1, 2009; 174(3): 989 - 998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Greenberg Proposed immunologic models of the inflammatory myopathies and potential therapeutic implications Neurology, November 20, 2007; 69(21): 2008 - 2019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Salajegheh, G. Rakocevic, R. Raju, A. Shatunov, L. G. Goldfarb, and M. C. Dalakas T cell receptor profiling in muscle and blood lymphocytes in sporadic inclusion body myositis Neurology, October 23, 2007; 69(17): 1672 - 1679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Bradshaw, A. Orihuela, S. L. McArdel, M. Salajegheh, A. A. Amato, D. A. Hafler, S. A. Greenberg, and K. C. O'Connor A Local Antigen-Driven Humoral Response Is Present in the Inflammatory Myopathies J. Immunol., January 1, 2007; 178(1): 547 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Shared Blood and Muscle CD8+ T-Cell Expansion in Inclusion Body Myositis Journal Watch Neurology, June 8, 2006; 2006(608): 8 - 8. [Full Text]
|
|