NEOPLASIA Expansion of CMV-specific CD8CD45RACD27 T cells in B-cell chronic lymphocytic leukemia

In patients with B-cell chronic lympho-cytic leukemia (B-CLL), the absolute num-ber of T cells is increased. Although it has been suggested that these T cells might be tumor specific, concrete evidence for this hypothesis is lacking. We performed a detailed immunophenotypic analysis of the T-cell compartment in the peripheral blood of 28 patients with B-CLL (Rai 0, n 12; Rai I-II, n 10; Rai III-IV, n 6) and 12 healthy age-matched controls and measured the ability of these patients to mount specific immune responses. In all Rai stages a significant increase in the absolute numbers of CD3 cells was ob-served. Whereas the number of CD4 cells was not different from controls, patients with B-CLL showed significantly increased relative and absolute numbers of CD8 cells, which exhibited a CD45RACD27 cyto-toxic phenotype. Analysis of specific immune responses with tetrameric cyto-megalovirus (CMV)–peptide complexes showed that patients with B-CLL had sig-nificantly increased numbers of tetramer-binding CMV-specific CD8 T cells. The rise in the total number of CD8 cytotoxic T cells was evident only in CMV-seroposi-tive B-CLL patients. Thus, our data sug-gest that in patients with B-CLL the com-position of T cells is shifted toward a CD8 cytotoxic cell type in an effort to control infections with persistent viruses such as CMV. Moreover, they offer an explanation for the high incidence of CMV reactivation in CLL patients treated with T cell–depleting agents, such as the mono-clonal antibody (mAb) alemtuzumab (Campath; -CD52 mAb). Furthermore, because in CMV-seronegative patients no increase in cytotoxic CD8 T cells is found, our studies do not support the hypothesis that tumor-specific T cells ac-count for T-cell expansion in B-CLL