OLIGOCLONALITY OF V-BETA-3 TCR CHAINS IN THE CD8(-CELL POPULATION OF RHEUMATOID-ARTHRITIS PATIENTS() T)

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 a ccompanied by rheumatoid arthritis, Felty's syndrome, or both, Therefo re, to identify disease-related alterations in the CD8(+) T cell reper toire, we have compared the patterns of oligoclonality in the CD8+ T c ells of rheumatoid arthritis patients (n = 32) with those of age-match ed controls (n = 25), By using a multiplex PCR assay for the CDR3 leng th of TCR p-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 c ompared with 4% of controls (p < 0.0002), In addition, two unrelated R A 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 patie nts usually, but not exclusively, involving the CD57(+) subset, These data define a phenotype of the T cell repertoire that is strongly asso ciated with rheumatoid arthritis; the mechanisms and genetic and envir onmental factors that explain this phenomenon remain to be defined.