Characterization of the T cell receptor repertoire in the Japanese neuromyelitis optica: T cell activity is up-regulated compared to multiple sclerosis.
To characterize T cell immunity in Japanese neuromyelitis optica (NMO), we examined the T cell receptor (TCR) repertoire in NMO patients with complementarity-determining region 3 (CDR3) spectratyping and compared the results with those from multiple sclerosis (MS) patients and healthy subjects. Both NMO and MS patients had a larger number of clonally expanded Vbeta genes than healthy subjects. Moreover, NMO patients had a significantly larger number of expanded Vbetas than MS patients. The detailed analysis revealed that Vbeta1 and Vbeta13 were significantly activated in NMO than MS. These results reflected unique pathophysiology of Japanese NMO, which is distinguishable from that of MS. Furthermore, longitudinal examinations of the TCR repertoire demonstrated that the number of clonally expanded Vbetas in NMO correlates with the Kurtzke Expanded disability status scale (EDSS). Although the activation pattern of the TCR repertoire in relapsing-remitting MS (RRMS) was similar to that in NMO, secondary progressive MS (SPMS) patients with longer disease durations and higher EDSS scores consistently had a smaller number of clonally expanded Vbetas than RRMS patients. Detailed TCR investigations will provide useful information to evaluate the clinical and immunological status of NMO and MS and to develop effective immunotherapies.
Warabi
Yoko
Y
Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan.
Yagi
Kohichi
K
Hayashi
Hideaki
H
Matsumoto
Yoh
Y
D000328:Adult; D000368:Aged; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D007111:Immunity, Cellular; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007564:Japan; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000208:ethnology / Q000276:immunology*; D009471:Neuromyelitis Optica / Q000188:drug therapy / Q000208:ethnology / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology
D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta