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Prepublished online as a Blood First Edition Paper on October 3, 2002; DOI 10.1182/blood-2002-03-0746.
Submitted March 11, 2002
Accepted August 27, 2002
Leukemia-associated monoclonal/oligoclonal TCR-BV usage in patients with B-cell chronic lymphocytic leukemia
Mohammad-Reza Rezvany, Mahmood Jeddi-Tehrani, Hans Wigzell, Anders Osterborg, and Hakan Mellstedt*
Immune and Gene Therapy Lab, Cancer Center Karolinska, Stockholm, Sweden
Immune and Gene Therapy Lab, Cancer Center Karolinska, Stockholm, Sweden; Department of Oncology, Karolinska Hospital, Stockholm, Sweden; Department of Immunology, Avesina Research Center, Tehran, Iran
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden
Immune and Gene Therapy Lab, Cancer Center Karolinska, Stockholm, Sweden; Department of Oncology, Karolinska Hospital, Stockholm, Sweden; Center for Hematology, Karolinska Hospital, Stockholm, Sweden
* Corresponding author; email: hakan.mellstedt{at}ks.se.
TCR-BV (T cell receptor B variable) gene usage and the CDR3 size distribution pattern were analyzed by RT-PCR in B-CLL patients to assess the T cell repertoire. The usage of TCR-BV families in CD4 and CD8 T cells stimulated with autologous activated leukemic cells was compared to that of freshly obtained blood T cells. Overexpression of individual TCR-BV families was found in freshly isolated CD4 and CD8 T cells. Poly-, oligo-, and/or monoclonal TCR-CDR3 patterns were seen within such overexpressed native CD4 and CD8 TCR-BV families. In non-overexpressed TCR-BV families mono/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 towards a mono/oligoclonal profile whereas largely monoclonal patterns in native overexpressed TCR-BV subsets remained monoclonal. 3/4 CD8 expansions found in freshly obtained CD8 T cells did further expand upon 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 1/9 expansions continued to further expand. Our data suggest that leukemia cell specific memory CD4 and CD8 T cells are present in vivo of CLL-patients and 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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