CDR3 spectratyping analysis of the TCR repertoire in myasthenia gravis.
Because myasthenia gravis (MG) is an autoimmune disease mediated by Abs specific for the acetylcholine receptor, helper T cells play a role in Ab production. In this study, we have performed large-scale cross-sectional and longitudinal TCR studies by CDR3 spectratyping using PBL and thymus tissues from MG patients. We found that there was no preferential usage of any particular TCR beta-chains that was identical among MG patients. However, the longitudinal study clearly demonstrated that one or more TCR Vbeta expansions persisted frequently in MG patients. Importantly, persistent TCR expansions correlated with clinical severity and high anti-acetylcholine receptor Ab titer. Finally, examinations of T cells expressing CXCR5, i.e., follicular B-helper T cells, revealed that spectratype expansions in MG patients were detected mainly in the CD4+ CXCR5+ T cell populations, whereas CD8+ T cells were the major source of clonal expansion in healthy subjects. These findings suggest that persistent clonal expansions of T cells in MG patients are associated with the development and maintenance of MG. Close examination of pathogenic T cells in MG provides useful information to elucidate the pathogenesis and to estimate the disease status.
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan. matyoh@tmin.ac.jp
Yoh
Y
Matsumoto
Hidenori
H
Matsuo
Hiroshi
H
Sakuma
Il-Kwon
IK
Park
Yukiko
Y
Tsukada
Kuniko
K
Kohyama
Takayuki
T
Kondo
Satoshi
S
Kotorii
Noritoshi
N
Shibuya
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D022801:Complementarity Determining Regions / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000235:genetics* / Q000276:immunology*; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology
C095085:CXCR5 protein, human; D022801:Complementarity Determining Regions; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine