CLONAL EXPANSION WITHIN THE CD4(-CELL SUBSETS IN CHRONIC LYMPHOCYTIC-LEUKEMIA()CD57(+) AND CD8(+)CD57(+) T)

The role of T cells in chronic lymphocytic leukemia (CLL) has not been extensively investigated, since the most prominent cellular abnormali ty in CLL involves the clonal expansion of B cells. In this study we h ave undertaken a comprehensive analysis of the CD4(+) and CD8(+) T cel l repertoire in a population of CLL patients (n = 19) and age-matched controls (n = 22), The TCR repertoire analysis was performed using a m ultiplex PCR assay for CDR3 length, an approach that allows for the de tection of underlying -oligoclonality in complex T cell populations. W e established that oligoclonality was substantially more frequent in b oth the CD4(+) and CD8(+) T cell populations of CLL patients than in t he age-matched controls (p < 0.001), Using three-color FAGS analysis w ith a panel of TCRV segment-specific mAbs, we also established that ol igoclonal expansions are predominantly found in the CD57(+) subset of both the CD4(+) and CD8(+) T cell populations. The frequency of the CD 57 marker on CD4(+) T cells was increased in the setting of CLL (% CD5 7 = 14.8 + 13.0%) compared with that in normal controls (% CD57 = 3.3 +/- 3.0%; p < 0.001). An elevated frequency of CD4(+)CD57(+) T cells w as correlated with more advanced disease. Similarly, the most extreme oligoclonal expansions of CD4(+)CD57(+) T cells occurred in CLL patien ts who had progressed beyond pal stage 0. These data document profound alterations in the T cell repertoire of CLL patients and point to a r ole for clonal T cell populations in the pathogenesis of this disease.