Expansion of effector T cells associated with decreased PD-1 expression in patients with indolent B cell lymphomas and chronic lymphocytic leukemia

Abstract

In patients with chronic lymphocytic leukemia (CLL), numbers of CD8 + CD45RA +/− CD27− effector T cells are expanded. We investigated whether this expansion is also present in other B cell malignancies and the possible mechanism underlying these changes. Whereas an increase in total CD4+and CD8+ T cell numbers was found only in CLL, numbers of CD4+ and CD8+ effector T cells were significantly increased in both CLL and indolent lymphoma, but not aggressive lymphoma and myeloma. Interestingly, PD-1 expression was decreased on effector T cells and inversely correlated with effector T cell numbers, suggesting a functional role for PD-1 in regulating T cell homeostasis. In vitro experiments revealed impaired up-regulation of PD-1 upon T cell activation in the presence of malignant but also healthy B cells. Our data suggest that in CLL and indolent lymphoma, the malignant B cells affect PD-1 expression on effector T cells, resulting in an expansion of these subsets.

Keywords::

• Effector T cells
• B cell non-Hodgkin lymphoma
• CLL
• CMV
• PD-1

Acknowledgements

This work was supported by a personal grant from the Dutch Cancer Society (UVA 2006–3712) to Sanne H. Tonino. The authors would like to thank J. M. Kerst, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute and W. E. Terpstra, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands for including patients in this study; P.A. Baars, Department of Experimental Immunology and J. A. Dobber, Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands for technical assistance; and K. C. Wolthers, Department of Virology, Academic Medical Center, Amsterdam, The Netherlands for performing viral diagnostics.

Potential conflict of interest

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