Oligoclonality of V beta 3 TCR chains in the CD8+ T cell population of rheumatoid arthritis patients.
It has been established that oligoclonal expansion is a common feature of the CD8+ T cell population, particularly within the CD8+ CD57+ lymphocyte subset. In addition, clonal malignancies involving CD8+ CD57+ T cells (large granulocytic lymphocytic leukemias) are often accompanied by rheumatoid arthritis, Felty's syndrome, or both. Therefore, to identify disease-related alterations in the CD8+ T cell repertoire, we have compared the patterns of oligoclonality in the CD8+ T cells of rheumatoid arthritis patients (n = 32) with those of age-matched controls (n = 25). By using a multiplex PCR assay for the CDR3 length of TCR beta-chains, we have found a striking increase in the frequency of CD8+ oligoclonality involving V beta 3 TCR: 50% of the rheumatoid arthritis patients had evidence of oligoclonality in this TCR family compared with 4% of controls (p < 0.0002). In addition, two unrelated RA patients had clonally dominant CD8+ T cell beta receptors that were identical in amino acid sequence, suggesting selection by a common Ag. An analysis of a subset of RA patients with mAbs specific for V beta 3 TCR revealed the presence of clonal expansion in a minority of patients usually, but not exclusively, involving the CD57+ subset. These data define a phenotype of the T cell repertoire that is strongly associated with rheumatoid arthritis; the mechanisms and genetic and environmental factors that explain this phenomenon remain to be defined.
Department of Medicine, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030, USA.
R
R
Hingorani
J
J
Monteiro
R
R
Furie
E
E
Chartash
C
C
Navarrete
R
R
Pergolizzi
P K
PK
Gregersen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001483:Base Sequence; D018959:CD57 Antigens / Q000032:analysis; D019070:Cell Lineage; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology
D018959:CD57 Antigens; D006680:HLA Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta