Brain, Vol. 123, No. 10, 2030-2039,
October 2000
© 2000 Oxford University Press
Clonal restriction of T-cell receptor expression by infiltrating lymphocytes in inclusion body myositis persists over time
Studies in repeated muscle biopsies
Neuromuscular Disease Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
Correspondence to:
Marinos C. Dalakas, MD, Neuromuscular Diseases Section, NINDS, National Institutes of Health, Building 10, Room 4N248, 10 Center Drive MSC 1382, Bethesda MD 20892-1382, USA E-mail: dalakas{at}helix.nih.gov
Inclusion body myositis (IBM) is an inflammatory myopathy characterized immunohistologically by prominent invasion of the non-necrotic, MHC-I class antigen-expressing muscle fibres by CD8+ cytotoxic T cells. If the autoinvasive CD8+ T cells are recruited specifically to the muscle and play a primary pathogenetic role in the disease, a clonal restriction persisting over time should be anticipated. In this study, we analysed the T-cell receptor (TCR) gene usage by endomysial T lymphocytes in three sequential muscle biopsies from three different IBM patients over a 19–22 month period using immunohistochemistry, reverse transcription–polymerase chain reaction (RT-PCR) and sequence analysis of the complementarity determining region (CDR3) of the amplified TCRs. We found that CD8+ T lymphocytes persist in the endomysial infiltrates in all biopsies during a 19–22 month period. The most frequently detected TCRs were the Vß3, Vß5.1, Vß6.7 and Vß13 gene families, and several of the autoinvasive CD8+ T cells expressed the TCRs Vß6.7 and Vß5.1. A restricted usage of the examined Vß6 gene family was found to persist in the complementarity CDR3 determining region of the autoinvasive T cells over the 22 month period. Identical Vß6 CDR3 gene arrangements were also found in the multiple muscle biopsies from two of the three IBM patients. The results indicate that in IBM there is a restricted expression of the TCR gene families among the autoinvasive T lymphocytes with homologies in the CDR3 region that persist over the course of the disease. A continuous, antigen-driven T-cell response is prominent in the muscle of patients with IBM.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A A Amato and R J Barohn Inclusion body myositis: old and new concepts J. Neurol. Neurosurg. Psychiatry, November 1, 2009; 80(11): 1186 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A Greenberg How citation distortions create unfounded authority: analysis of a citation network BMJ, July 23, 2009; 339(jul20_3): b2680 - b2680. [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]
|
|
|
|
 |
|
 D. Dimitri, O. Benveniste, O. Dubourg, T. Maisonobe, B. Eymard, Z. Amoura, L. Jean, K. Tiev, J.-C. Piette, D. Klatzmann, et al. Shared blood and muscle CD8+ T-cell expansions in inclusion body myositis Brain, April 1, 2006; 129(4): 986 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Dalakas Inflammatory, immune, and viral aspects of inclusion-body myositis Neurology, January 24, 2006; 66(1_suppl_1): S33 - S38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yakushiji, J. Satoh, M. Yukitake, K. Yamaguchi, I. Nakamura, I. Nishino, and Y. Kuroda Interferon {beta}-responsive inclusion body myositis in a hepatitis C virus carrier Neurology, August 10, 2004; 63(3): 587 - 588. [Full Text] [PDF]
|
|
|
|
|
|
J. Schmidt, G. Rakocevic, R. Raju, and M. C. Dalakas Upregulated inducible co-stimulator (ICOS) and ICOS-ligand in inclusion body myositis muscle: significance for CD8+ T cell cytotoxicity Brain, May 1, 2004; 127(5): 1182 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. O'Keefe, M. Plasilova, M. Wlodarski, A. M. Risitano, A. R. Rodriguez, E. Howe, N. S. Young, E. Hsi, and J. P. Maciejewski Molecular Analysis of TCR Clonotypes in LGL: A Clonal Model for Polyclonal Responses J. Immunol., February 1, 2004; 172(3): 1960 - 1969. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hofbauer, S. Wiesener, H. Babbe, A. Roers, H. Wekerle, K. Dornmair, R. Hohlfeld, and N. Goebels Clonal tracking of autoaggressive T cells in polymyositis by combining laser microdissection, single-cell PCR, and CDR3-spectratype analysis PNAS, April 1, 2003; 100(7): 4090 - 4095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Randomized pilot trial of {beta}INF1a (Avonex) in patients with inclusion body myositis Neurology, November 13, 2001; 57(9): 1566 - 1570. [Abstract] [Full Text] [PDF]
|
|