Cancer Immunology, Immunotherapy

, Volume 62, Issue 11, pp 1697–1709 | Cite as

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

  • Joachim Rudolf Göthert
  • Lewin Eisele
  • Ludger Klein-Hitpass
  • Stefanie Weber
  • Marie-Louise Zesewitz
  • Ludger Sellmann
  • Alexander Röth
  • Hanspeter Pircher
  • Ulrich Dührsen
  • Jan Dürig
Original Article

Abstract

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.

Keywords

Chronic lymphocytic leukemia Gene set enrichment analysis CD8+ T cells KLRG1 

Supplementary material

262_2013_1473_MOESM1_ESM.pdf (748 kb)
Supplementary material 1 (PDF 747 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Joachim Rudolf Göthert
    • 1
  • Lewin Eisele
    • 1
  • Ludger Klein-Hitpass
    • 2
  • Stefanie Weber
    • 1
  • Marie-Louise Zesewitz
    • 1
  • Ludger Sellmann
    • 1
  • Alexander Röth
    • 1
  • Hanspeter Pircher
    • 3
  • Ulrich Dührsen
    • 1
  • Jan Dürig
    • 1
  1. 1.Department of Hematology, West German Cancer Center (WTZ)University Hospital EssenEssenGermany
  2. 2.Institute of Cell BiologyUniversity Hospital EssenEssenGermany
  3. 3.Department of Immunology, Institute of Medical Microbiology and HygieneUniversity of FreiburgFreiburgGermany

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