Autologous T lymphocytes may specifically recognize leukaemic B cells in patients with chronic lymphocytic leukaemia

V. Shalhoub, G. Elliott, L. Chiu, R. Manoukian, M. Kelley, N. Hawkins, E. Davy, G. Shimamoto, J. Beck, S. A. Kaufman, G. Van, S. Scully, M. Qi, M. Grisanti, C. Dunstan, W. J. Boyle, D. L. Lacey

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

This study analysed a naturally occurring specific cellular immunity against tumour cells in chronic lymphocytic leukaemia (CLL) patients. Five out of eight patients had blood T lymphocytes able to recognize spontaneously and specifically the autologous tumour B cells (proliferation assay). In these five patients, detection of cytokines by real-time reverse transcription polymerase chain reaction (RT-PCR) revealed that granulocyte-macrophage colony-stimulating factor (GM-CSF) was the most abundant cytokine gene expressed by the T cells that recognized the autologous tumour B cells. Other activated cytokine genes were γ-interferon (IFN), interleukin (IL)-2 and tumour necrosis factor (TNF)-α, but not IL-4. This profile suggests a type 1 anti-B-CLL T-cell response. CD80 and CD54 were relatively downregulated on the native tumour B cells compared with control normal B cells. Upregulation of CD80 on the leukaemic cells was mandatory for the induction of such a specific T-cell response. CD80 and CD54 monoclonal antibodies inhibited the specific T-cell DNA synthesis proliferation. The proliferative T-cell response was either MHC class I or class II restricted (inhibition by monoclonal antibodies). The specific cytokine gene expression could be found in isolated CD4, as well as CD8, T-cell subsets. This study demonstrated the presence of a potential natural specific CD4, as well as a CD8 type 1 T-cell immunity against the leukaemic CLL tumour B cells in CLL. A further detailed analysis of the spontaneous anti-CLL T-cell immunity is warranted that may facilitate the development of effective anti-tumour vaccines in CLL.

Original languageEnglish (US)
Pages (from-to)608-617
Number of pages10
JournalBritish journal of haematology
Volume111
Issue number2
DOIs
StatePublished - Dec 1 2000
Externally publishedYes

Keywords

  • B-CLL
  • Co-stimulatory molecules
  • Cytokines
  • Natural immunity
  • T cells

ASJC Scopus subject areas

  • Hematology

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    Shalhoub, V., Elliott, G., Chiu, L., Manoukian, R., Kelley, M., Hawkins, N., Davy, E., Shimamoto, G., Beck, J., Kaufman, S. A., Van, G., Scully, S., Qi, M., Grisanti, M., Dunstan, C., Boyle, W. J., & Lacey, D. L. (2000). Autologous T lymphocytes may specifically recognize leukaemic B cells in patients with chronic lymphocytic leukaemia. British journal of haematology, 111(2), 608-617. https://doi.org/10.1046/j.1365-2141.2000.02383.x