Leukemia-associated monoclonal and oligoclonal TCR-BV use in patients with B-cell chronic lymphocytic leukemia.
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.
Rezvany
Mohammad-Reza
MR
Immune and Gene Therapy Laboratory, Cancer Center Karolinska, the Department of Oncology (Radiumhemmet), Karolinska Hospital, Stockholm, Sweden.
Jeddi-Tehrani
Mahmood
M
Wigzell
Hans
H
Osterborg
Anders
A
Mellstedt
Håkan
H
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D018920:Coculture Techniques; D022801:Complementarity Determining Regions / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D019672:Genes, T-Cell Receptor; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012334:RNA, Neoplasm / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA
D022801:Complementarity Determining Regions; D012334:RNA, Neoplasm; D016693:Receptors, Antigen, T-Cell, alpha-beta