Original Manuscript

Leukemia (2005) 19, 835–840. doi:10.1038/sj.leu.2403704 Published online 03 March 2005

Immunology

CD56dimCD16neg cells are responsible for natural cytotoxicity against tumor targets

This work was supported by a grant of the Deutsche Krebshilfe.

O Penack1, C Gentilini1, L Fischer1, A M Asemissen1, C Scheibenbogen1, E Thiel1 and L Uharek1

1Department of Hematology, Oncology, and Transfusion Medicine, Charité-Campus Benjamin Franklin, Berlin, Germany

Correspondence: Dr O Penack, Department of Hematology, Oncology, and Transfusion Medicine, Charité-Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. Fax: +49-30-8445-3395; E-mail: olaf.penack@charite.de

Received 27 October 2004; Accepted 7 December 2004; Published online 3 March 2005.

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Abstract

The activation of natural killer (NK) cells leads to degranulation and secretion of cytotoxic granula. During this process, the lytic granule membrane protein CD107a becomes detectable at the cell surface. Based on this phenomenon, we have analyzed by a novel flow cytometry-based assay, the number and phenotype of NK cells responding to tumor targets. Using human leukemia and lymphoma cell lines, we observed a close correlation between CD107a surface expression and target cell lysis, indicating that NK cell cytotoxicity can be assessed by this method. The number of degranulating NK cells was closely related to the ratio of effector and target cells and showed a maximum at a ratio of 1:1. Moreover, we were able to show that the population of CD56dim/CD16neg NK cells is primarily responsible for the cytotoxic activity against tumor targets whereas neither CD56dim/CD16pos nor CD56bright NK cells degranulated in response to the cell lines. Our results indicate that the CD107a assay represents a promising new method for the quantification and characterization of cells exhibiting natural cytotoxicity.

Keywords:

NK cell, CD107a, flow cytometry, degranulation, activity

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