Clonal expansion within the CD4(+)CD57(+) and CD8(+)CD57(+) T cell subsets in chronic lymphocytic leukemia

The role of T cells in chronic lymphocytic leukemia (CLL) has not been extensively investigated, since the most prominent cellular abnormality in CLL involves the clonal expansion of B cells. In this study we have undertaken a comprehensive analysis of the CD4(+) and CD8(+) T cell repertoire in a population of CLL patients (n = 19) and age-matched controls (n = 22), The TCR repertoire analysis was performed using a multiplex PCR assay for CDR3 length, an approach that allows for the detection of underlying -oligoclonality in complex T cell populations. We established that oligoclonality was substantially more frequent in both the CD4(+) and CD8(+) T cell populations of CLL patients than in the age-matched controls (p < 0.001), Using three-color FAGS analysis with a panel of TCRV segment-specific mAbs, we also established that oligoclonal expansions are predominantly found in the CD57(+) subset of both the CD4(+) and CD8(+) T cell populations. The frequency of the CD57 marker on CD4(+) T cells was increased in the setting of CLL (% CD57 = 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 was correlated with more advanced disease. Similarly, the most extreme oligoclonal expansions of CD4(+)CD57(+) T cells occurred in CLL patients who had progressed beyond pal stage 0. These data document profound alterations in the T cell repertoire of CLL patients and point to a role for clonal T cell populations in the pathogenesis of this disease.