Expanded CD8+ T cells of murine and human CLL are driven into a senescent KLRG1+ effector memory phenotype

Cancer Immunol Immunother. 2013 Nov;62(11):1697-1709. doi: 10.1007/s00262-013-1473-z.


Altered numbers and functions of T cells have previously been demonstrated in chronic lymphocytic leukemia (CLL) patients. However, dynamics and specific T-cell subset alterations have not been studied in great detail. Therefore, we studied CLL blood lymphocyte subsets of individual patients in a longitudinal manner. Dynamic expansions of blood CD4 + and CD8 + T-cell numbers were consistently associated with a progressively increasing CLL leukemic compartment. Interestingly, the T-cell subset expansion over time was more pronounced in CD38 + CLL. Additionally, we performed gene expression profiling of CD3 + T cells of CLL patients and normal donors. Using gene set enrichment analysis, we found significant enrichment of genes with higher expression in CLL T cells within CD8+ effector memory and terminal effector T-cell gene signatures. In agreement with these data, we observed a marked expansion of phenotypic CD8 + effector memory T cells in CLL by flow cytometry. Moreover, we observed that increments of CD8 + effector memory T cells in human CLL and also mouse CLL (Eμ-TCL1 model) were due to an expansion of the inhibitory killer cell lectin-like receptor G1 (KLRG1) expressing cellular subset. Furthermore, higher plasma levels of the natural KLRG1 ligand E-cadherin were detected in CLL patients compared to normal donor controls. The predominance of KLRG1+ expression within CD8+ T cells in conjunction with increased systemic soluble E-cadherin might significantly contribute to CLL immune dysfunction and might additionally represent an important component of the CLL microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cadherins / genetics
  • Cadherins / immunology
  • Cadherins / metabolism
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cell Proliferation
  • Female
  • Flow Cytometry
  • Humans
  • Immunologic Memory / genetics
  • Immunologic Memory / immunology*
  • Immunophenotyping
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology*
  • Lectins, C-Type / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Receptors, Immunologic / metabolism
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / immunology*
  • Trans-Activators / metabolism
  • Transcriptome / genetics
  • Transcriptome / immunology


  • Cadherins
  • KLRG1 protein, human
  • Klrg1 protein, mouse
  • Lectins, C-Type
  • Receptors, Immunologic
  • Trans-Activators

Associated data

  • GEO/GSE19147