Research Papers:

CD1d expression on chronic lymphocytic leukemia B cells affects disease progression and induces T cell skewing in CD8 positive and CD4CD8 double negative T cells

Nadja Zaborsky _, Franz Josef Gassner, Daniela Asslaber, Petra Reinthaler, Ursula Denk, Sabine Flenady, Josefina Piñón Hofbauer, Barbara Danner, Stefan Rebhandl, Andrea Harrer, Roland Geisberger, Richard Greil and Alexander Egle

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Oncotarget. 2016; 7:49459-49469. https://doi.org/10.18632/oncotarget.10372

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Nadja Zaborsky1,2, Franz Josef Gassner1,2, Daniela Asslaber1,2, Petra Reinthaler1,2, Ursula Denk1,2, Sabine Flenady1,2, Josefina Piñón Hofbauer1,2, Barbara Danner1,2, Stefan Rebhandl1,2, Andrea Harrer3, Roland Geisberger1,2, Richard Greil1,2, Alexander Egle1,2

1Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria

2Salzburg Cancer Research Institute, Salzburg, Austria

3Department of Neurology, Paracelsus Medical University, Salzburg, Austria

Correspondence to:

Nadja Zaborsky, email: [email protected]

Keywords: CLL, T cells, T cell skewing, CD1d, CD161

Received: August 25, 2015     Accepted: June 16, 2016     Published: July 01, 2016


Chronic lymphocytic leukemia develops within a complex network driven by genetic mutations and microenvironmental interactions. Among the latter a complex interplay with the immune system is established by the clone. Next to a proposed recruitment of support from T and myeloid cells, potential anti-CLL immune reactions need to be subverted.

By using TCL1 mice as a CLL model, we show that TCR-Vβ7+ NK1.1+ T cells are overrepresented in this disease model and constitute a main subset of peripheral CD3+ cells with biased TCR usage, showing that these cells account for a major part for T cell skewing in TCL1 mice. Moreover, we show that overrepresentation is dependent on CD1d expression in TCL1 mice, implicating that these cells belong to a NKT-like cell fraction which are restricted to antigen presented by the MHC-like surface marker CD1d. Accordingly, we observed a high fraction of CD161+ cells within overrepresented T cells in CLL patients and we found downregulation of CD1d on the surface of CLL cells, both in TCL1 mice and patients. Finally, we show that in TCL1 mice, CD1d deficiency resulted in shortened overall survival. Our results point to an interaction between CLL and CD161+ T cells that may represent a novel therapeutic target for immune modulation.

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