Chronic lymphocytic leukaemia induces an exhausted T cell phenotype in the TCL1 transgenic mouse model

Br J Haematol. 2015 Aug;170(4):515-22. doi: 10.1111/bjh.13467. Epub 2015 May 4.


Although chronic lymphocytic leukaemia (CLL) is a B cell malignancy, earlier studies have indicated a role of T cells in tumour growth and disease progression. In particular, the functional silencing of antigen-experienced T cells, called T cell exhaustion, has become implicated in immune evasion in CLL. In this study, we tested whether T cell exhaustion is recapitulated in the TCL1(tg) mouse model for CLL. We show that T cells express high levels of the inhibitory exhaustion markers programmed cell death 1 (PDCD1, also termed PD-1) and lymphocyte-activation gene 3 (LAG3), whereas CLL cells express high levels of CD274 (also termed PD-ligand 1). In addition, the fraction of exhausted T cells increases with CLL progression. Finally, we demonstrate that exhausted T cells are reinvigorated towards CLL cytotoxicity by inhibition of PDCD1/CD274 interaction in vivo. These results suggest that T cell exhaustion contributes to CLL pathogenesis and that interference with PDCD1/CD274 signalling holds high potential for therapeutic approaches.

Keywords: PDCD1; T cell exhaustion; chemoimmunotherapy; chronic lymphocytic leukaemia; tumour surveillance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation, Leukemic / genetics
  • Gene Expression Regulation, Leukemic / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Mice
  • Mice, Transgenic
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology*
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / pathology
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology


  • Neoplasm Proteins