Leukemia-associated monoclonal and oligoclonal TCR-BV use in patients with B-cell chronic lymphocytic leukemia

Blood. 2003 Feb 1;101(3):1063-70. doi: 10.1182/blood-2002-03-0746. Epub 2002 Oct 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Case-Control Studies
  • Coculture Techniques
  • Complementarity Determining Regions / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / immunology
  • Genes, T-Cell Receptor*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Lymphocyte Activation
  • Middle Aged
  • Polymorphism, Genetic
  • RNA, Neoplasm / analysis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, RNA

Substances

  • Complementarity Determining Regions
  • RNA, Neoplasm
  • Receptors, Antigen, T-Cell, alpha-beta