Journal article

HIV inhibits early signal transduction events triggered by CD16 cross-linking on NK cells, which are important for antibody-dependent cellular cytotoxicity

Gregor F Lichtfuss, Aislin C Meehan, Wan-Jung Cheng, Paul U Cameron, Sharon R Lewin, Suzanne M Crowe, Anthony Jaworowski

Journal of Leukocyte Biology | WILEY | Published : 2011

Abstract

Measurement of NK cell cytolytic activity in the setting of chronic viral infection is important for determining viral pathogenicity. Mobilization of LAMP-1 (CD107a) to the NK cell surface is a surrogate marker for cytotoxic granule release and hence, NK cell cytotoxicity. We have developed a convenient, rapid, whole blood flow cytometric assay for measuring CD107a mobilization in response to CD16 cross-linking, a surrogate for NK cell ADCC activity ex vivo, which can be performed using small volumes of patient whole blood. Using this assay, we show that CD107a mobilization, in response to CD16 cross-linking, is triggered in CD56(dim) but not CD56(bright) NK cells, requiring Syk/Zap70 tyrosi..

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Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC)


Funding Acknowledgements

This study was funded through the National Health and Medical Research Council of Australia (NHMRC), project grant 543137. We thank Prof. Mark Hogarth for donating the anti-CD16 antibody, Cath Downs and the clinical research nursing staff of the Infectious Diseases Unit, The Alfred Hospital, for patient recruitment, and all participants and blood donors for the HiACT study. Further, we thank Dr. Marjon Navis, University of Melbourne, for constructive and critical discussion of the results.