Laboratoire Francais Of Fractionnement Et Des Biotechnologies Lfb

Les Ulis, France

Laboratoire Francais Of Fractionnement Et Des Biotechnologies Lfb

Les Ulis, France
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Le Garff-Tavernier M.,French Institute of Health and Medical Research | Le Garff-Tavernier M.,University Pierre and Marie Curie | Beziat V.,French Institute of Health and Medical Research | Beziat V.,University Pierre and Marie Curie | And 13 more authors.
Aging Cell | Year: 2010

Aging is generally associated with an increased predisposition to infectious diseases and cancers, related in part to the development of immune senescence, a process that affects all cell compartments of the immune system. Although many studies have investigated the effects of age on natural killer (NK) cells, their conclusions remain controversial because the diverse health status of study subjects resulted in discordant findings. To clarify this situation, we conducted the first extensive phenotypic and functional analysis of NK cells from healthy subjects, comparing NK cells derived from newborn (cord blood), middle-aged (18-60 years), old (60-80 years), and very old (80-100 years) subjects. We found that NK cells in cord blood displayed specific features associated with immaturity, including poor expression of KIR and LIR-1/ILT-2 and high expression of both NKG2A and IFN-γ. NK cells from older subjects, on the other hand, preserved their major phenotypic and functional characteristics, but with their mature features accentuated. These include a profound decline of the CD56 bright subset, a specific increase in LIR-1/ILT-2, and a perfect recovering of NK-cell function following IL2-activation in very old subjects. We conclude that the preservation of NK cell features until very advanced age may contribute to longevity and successful aging. © The Authors Journal compilation. © Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland 2010.


Le Garff-Tavernier M.,French Institute of Health and Medical Research | Le Garff-Tavernier M.,University Pierre and Marie Curie | Decocq J.,French Institute of Health and Medical Research | Decocq J.,University Pierre and Marie Curie | And 22 more authors.
Leukemia | Year: 2011

Although anti-CD20 monoclonal antibodies (mAbs) show promise for the treatment of chronic lymphocytic leukemia (CLL), the success of the anti-CD20 mAb rituximab in CLL treatment has been limited. Novel anti-CD20 mAbs with more potent cytotoxic activity have recently been engineered, but so far most have only been tested in vitro with natural killer (NK) cells from healthy donors. Because it is still unclear whether these optimized cytotoxic mAbs will improve NK-cell killing of tumor cells in CLL patients, we characterized the relevant phenotypic and functional features of NK cells from CLL patients in detail. Expression of inhibitory and activating NK-cell receptors and of Fc gamma receptor IIIA (FcγRIIIA) is well preserved in CD16 CD56dim cytotoxic NK cells from these patients, independently of disease progression. These cells are fully functional following cytokine stimulation. In addition, the FcγRIIIA-optimized LFB-R603 anti-CD20 mAb mediates 100 times greater antibody-dependent cell-mediated cytotoxicity by NK cells from CLL patients and healthy donors than rituximab. Enhanced degranulation against autologous B-CLL cells is observed at lower concentrations of LFB-R603 than rituximab, regardless of CLL prognostic factors. These findings strongly justify further clinical development of anti-CD20 mAbs optimized for FcγR engagement in CLL patients. © 2011 Macmillan Publishers Limited All rights reserved.

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