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Prepublished online as a Blood First Edition Paper on April 10, 2003; DOI 10.1182/blood-2003-01-0182.

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Submitted January 21, 2003
Accepted April 1, 2003

Expansion of CMV-specific CD8+CD45RA+CD27- T cells in B-cell chronic lymphocytic leukemia

Wendelina J Mackus, Florine N Frakking, Annette Grummels, Laila E Gamadia, Godelieve J De Bree, Dorte Hamann, Rene A Van Lier, and Marinus H Van Oers*

Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

* Corresponding author; email: m.h.vanoers{at}amc.uva.nl.

In B-CLL patients the absolute number 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 immunophenotypical analysis of the T cell compartment in the peripheral blood of 28 B-CLL patients (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 observed. Whereas the number of CD4+ cells was not different from controls, B-CLL patients showed significantly increased relative and absolute numbers of CD8+ cells which exhibited a CD45RA+CD27- cytotoxic phenotype. Analysis of specific immune responses with tetrameric CMV-peptide complexes showed that B-CLL patients had significantly increased numbers of tetramer-binding CMV-specific CD8+ T cells. The rise in the total number of CD8+ cytotoxic T cells was only evident in CMV-seropositive B-CLL patients. Thus, our data suggest that in B-CLL patients the composition of T cells is shifted towards 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 MabCampath ({alpha}-CD52 mAb). Furthermore, since 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 account for T cell expansion in B-CLL.


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