OLIGOCLONAL CD4(-CELL EXPANSIONS CONTRIBUTE TO THE IMBALANCED T-CELL RECEPTOR REPERTOIRE OF RHEUMATOID-ARTHRITIS PATIENTS()CD57(+) T)

A peculiar feature of rheumatoid arthritis patients is that they carry clonally expanded CD4(+) and CD8(+) cells in the peripheral blood. Wh ile the distortion of the repertoire of CD8(+) cells has been ascribed to the increase of CD8(+)CD57(+) large granular lymphocytes, often de tected in these patients, the mechanism responsible for the clonal exp ansion of CD4(+) cells remains unexplained. Here, we report that CD4()CD57(+) cells, that in healthy individuals represent a small subset o f peripheral CD4(+) lymphocytes, are significantly expanded in the per ipheral blood of a considerable percentage of rheumatoid arthritis pat ients. Furthermore, the expansion of these lymphocytes appears to corr elate with the presence of rheumatoid factor. The molecular analysis o f the T-cell receptor variable beta segments expressed by the CD4(+)CD 57(+) cells enriched in rheumatoid arthritis patients showed that they use restricted repertoires, that partially overlap with those of thei r CD4(-)CD57(+) counterpart. The structural feature of the receptor li gand expressed by these cells revealed that their expansion is most li kely mediated by strong antigenic pressures. However, since we also fo und that CD4(+)CD57(+) and CD4(-)CD57(+) cells can share the same clon al specificity, it is likely that their selection is not mediated by c onventional major histocompatibility complex restricted mechanisms. Th us, while our data demonstrate that CD4(+)CD57(+) cells play an import ant role in establishing the imbalance of the CD4(+) cell repertoire o bserved in rheumatoid arthritis patients, they also suggest that these cells have common features with mouse CD4(+)CD8(-)NK1.1(+)/T cells. ( C) 1997 by The American Society of Hematology.