title: Interleukin-21 and rituximab enhance NK cell functionality in patients with B-cell chronic lymphocytic leukaemia.
abstract: We have examined natural killer (NK) cell functionality of 54 B-CLL patients upon in vitro stimulation with interleukin-21 (IL-21), together with the anti-CD20 antibody, rituximab. Upon stimulation with rituximab-coated target cells IFN-γ production was reduced in patients' NK cells compared to healthy donors', while both natural- and antibody-dependent cytotoxicity (ADCC) was normal. Following additional stimulation with IL-21, IFN-γ production, natural cytotoxicity and ADCC were significantly augmented in patients. A complete restoration of IFN-γ production, however, required the depletion of malignant cells prior to stimulation. Collectively, our data show that NK cells of B-CLL patients are reversibly inhibited, but that their functionality can be normalized by stimulation with IL-21 and when inhibitory effects of the malignant B-CLL cells are eliminated by depletion.
authors.affiliation: Institute of Medical Microbiology and Immunology, Aarhus University, and Department of Haematology, Aarhus University Hospital, Aarhus, Denmark. christianeskelund@gmail.com
authors.forename: Christian W
authors.initials: CW
authors.lastname: Eskelund
authors.forename: Line
authors.initials: L
authors.lastname: Nederby
authors.forename: Anna H
authors.initials: AH
authors.lastname: Thysen
authors.forename: Anni
authors.initials: A
authors.lastname: Skovbo
authors.forename: Anne S
authors.initials: AS
authors.lastname: Roug
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Hokland
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D000098546:Interleukin-21
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D007378:Interleukins; D000069283:Rituximab; D007371:Interferon-gamma; D000098546:Interleukin-21