Oligoclonal CD4(+)CD57(+) T-cell expansions contribute to the imbalanced T-cell receptor repertoire of rheumatoid arthritis patients

A peculiar feature of rheumatoid arthritis patients is that they carry clonally expanded CD4(+) and CD8(+) cells in the peripheral blood. While the distortion of the repertoire of CD8(+) cells has been ascribed to the increase of CD8(+)CD57(+) large granular lymphocytes, often detected in these patients, the mechanism responsible for the clonal expansion of CD4(+) cells remains unexplained. Here, we report that CD4(+)CD57(+) cells, that in healthy individuals represent a small subset of peripheral CD4(+) lymphocytes, are significantly expanded in the peripheral blood of a considerable percentage of rheumatoid arthritis patients. Furthermore, the expansion of these lymphocytes appears to correlate with the presence of rheumatoid factor. The molecular analysis of the T-cell receptor variable beta segments expressed by the CD4(+)CD57(+) cells enriched in rheumatoid arthritis patients showed that they use restricted repertoires, that partially overlap with those of their CD4(-)CD57(+) counterpart. The structural feature of the receptor ligand expressed by these cells revealed that their expansion is most likely mediated by strong antigenic pressures. However, since we also found that CD4(+)CD57(+) and CD4(-)CD57(+) cells can share the same clonal specificity, it is likely that their selection is not mediated by conventional major histocompatibility complex restricted mechanisms. Thus, while our data demonstrate that CD4(+)CD57(+) cells play an important role in establishing the imbalance of the CD4(+) cell repertoire observed 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.