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01-11-2013 | Original Article

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

Authors: Joachim Rudolf Göthert, Lewin Eisele, Ludger Klein-Hitpass, Stefanie Weber, Marie-Louise Zesewitz, Ludger Sellmann, Alexander Röth, Hanspeter Pircher, Ulrich Dührsen, Jan Dürig

Published in: Cancer Immunology, Immunotherapy | Issue 11/2013

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.

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Title: Expanded CD8+ T cells of murine and human CLL are driven into a senescent KLRG1+ effector memory phenotype
Authors: Joachim Rudolf Göthert
Lewin Eisele
Ludger Klein-Hitpass
Stefanie Weber
Marie-Louise Zesewitz
Ludger Sellmann
Alexander Röth
Hanspeter Pircher
Ulrich Dührsen
Jan Dürig
Publication date: 01-11-2013
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 11/2013
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-013-1473-z

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