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Prepublished online as a Blood First Edition Paper on October 3, 2002; DOI 10.1182/blood-2002-03-0746.
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Blood, 1 February 2003, Vol. 101, No. 3, pp. 1063-1070
NEOPLASIA
Leukemia-associated monoclonal and oligoclonal TCR-BV use in
patients with B-cell chronic lymphocytic leukemia
Mohammad-Reza Rezvany,
Mahmood Jeddi-Tehrani,
Hans Wigzell,
Anders Österborg, and
Håkan Mellstedt
From the Immune and Gene Therapy Laboratory, Cancer
Center Karolinska, the Department of Oncology (Radiumhemmet), the
Microbiology and Tumorbiology Center, and the Center for Hematology,
Karolinska Hospital, Stockholm, Sweden; and the Department
of Immunology, Avesina Research Center, Tehran, Iran.
T-cell receptor-B-variable (TCR-BV) gene usage and
the CDR3 size distribution pattern were analyzed by reverse
transcription-polymerase chain reaction (RT-PCR) in patients with
B-cell chronic lymphocytic leukemia (B-CLL) to assess the T-cell
repertoire. The use of TCR-BV families in CD4 and CD8 T cells
stimulated with autologous activated leukemic cells was compared with
that of freshly obtained blood T cells. Overexpression of individual
TCR-BV families was found in freshly isolated CD4 and CD8 T cells.
Polyclonal, oligoclonal, and monoclonal TCR-CDR3 patterns were seen
within such overexpressed native CD4 and CD8 TCR-BV families. In
nonoverexpressed TCR-BV families, monoclonal and oligoclonal
populations were noted only within the CD8 subset. After in vitro
stimulation of T cells with autologous leukemic B cells, analyses of
the CDR3 length patterns showed that in expanded TCR-BV populations,
polyclonal patterns frequently shifted toward a monoclonal/oligoclonal
profile, whereas largely monoclonal patterns in native overexpressed
TCR-BV subsets remained monoclonal. Seventy-five percent of CD8
expansions found in freshly obtained CD8 T cells further expanded on in
vitro stimulation with autologous leukemic B cells. This suggests a
memory status of such cells. In contrast, the unusually high frequency
of CD4 T-cell expansions found in freshly isolated peripheral blood
cells did not correlate positively to in vitro stimulation as only 1 of
9 expansions continued to expand. Our data suggest that leukemia cell-specific memory CD4 and CD8 T cells are present in vivo of patients with CLL and that several leukemia cell-associated
antigens/epitopes are recognized by the patients' immune system,
indicating that whole leukemia cells might be of preference for vaccine development.
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