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

Leuk Lymphoma. 2012 Sep;53(9):1785-94. doi: 10.3109/10428194.2012.673224. Epub 2012 Apr 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Proliferation*
  • Cells, Cultured
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / metabolism
  • Cytomegalovirus Infections / pathology
  • Flow Cytometry
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Leukocyte Common Antigens / immunology
  • Leukocyte Common Antigens / metabolism
  • Lymphocyte Activation / immunology
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology
  • Middle Aged
  • Programmed Cell Death 1 Receptor / immunology*
  • Programmed Cell Death 1 Receptor / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology

Substances

  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Leukocyte Common Antigens