Chronic Lymphocytic Leukaemia Induces an Exhausted T Cell Phenotype in the TCL1 Transgenic Mouse Model

Overview

Journal Br J Haematol

Specialty Hematology

Date 2015 May 6

PMID 25940792

Citations 26

Authors

Franz J Gassner

Nadja Zaborsky

Kemal Catakovic

Stefan Rebhandl

Michael Huemer

Alexander Egle

Tanja N Hartmann

Richard Greil

Roland Geisberger

Affiliations

Soon will be listed here.

Abstract

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.

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