title: 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.
authors.affiliation: Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands. s.h.tonino@amc.nl
authors.forename: Sanne H
authors.initials: SH
authors.lastname: Tonino
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: van de Berg
authors.forename: Si La
authors.initials: SL
authors.lastname: Yong
authors.forename: Ineke J
authors.initials: IJ
authors.lastname: ten Berge
authors.forename: Marie José
authors.initials: MJ
authors.lastname: Kersten
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: Marinus H
authors.initials: MH
authors.lastname: van Oers
authors.forename: Arnon P
authors.initials: AP
authors.lastname: Kater
mesh_terms: D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D017493:Leukocyte Common Antigens