HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ortaldo, J. R. Articles by Ware, C. F. Search for Related Content PubMed PubMed Citation Articles by Ortaldo, J. R. Articles by Ware, C. F.

Journal of Leukocyte Biology, Vol 61, Issue 2 209-215, Copyright © 1997 by Society for Leukocyte Biology

JOURNAL ARTICLE

Fas involvement in human NK cell apoptosis: lack of a requirement for CD16-mediated events

JR Ortaldo, RT Winkler-Pickett, S Nagata and CF Ware
Division of Basic Sciences, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.

Propriocidal regulation of T cells refers to apoptosis induced by interleukin-2 (IL-2) activation with subsequent antigen receptor stimulation. We previously reported that natural killer (NK) cells also exhibit propriocidal death. Cell death can be induced following occupancy of the Fc gamma RIII (CD16) receptor when NK cells were pretreated with IL-2, IL-12, or IL-15. Here we show other triggering receptors on NK cells such as CD44, anti-NK-receptor antibodies, and pharmacological activation can result in the cell death signal. Requirement for cell interactions indicated that cell contact was required; however, unlike cell-mediated lysis, extracellular calcium was not required. Like T cells, the process of cell death for NK cells was receptor-induced apoptosis. Activation-induced apoptosis of T cells is mediated by members of the tumor necrosis factor (TNF) cytokine superfamily. We examined the involvement of TNF receptor family members or Fas in this rapid cell death. Antibody directed against Fas, TNFR60, TNFR80, LTBR, and LT alpha failed to inhibit receptor-induced death. Therefore, NK cells appear to demonstrate a rapid apoptotic episode when CD16 is cross-linked, but the mechanism of this apoptosis is quite different than was observed in T cells with CD3. The direct examination of the Fas pathway on activated NK cells revealed that susceptibility required longer treatment times and IL-2 activation. This susceptibility was paralleled by increased Fas-ligand expression. Therefore, NK cells can demonstrate an apoptotic response to CD16, CD44, NK receptors, and Fas. The enumeration of ligands capable of eliciting NK cell death and the in vivo relevance of this observation require further study.

This article has been cited by other articles:

				H. S. Warren and B. F. Kinnear Quantitative Analysis of the Effect of CD16 Ligation on Human NK Cell Proliferation J. Immunol., January 15, 1999; 162(2): 735 - 742. [Abstract] [Full Text] [PDF]

				T. Lamy, J. H. Liu, T. H. Landowski, W. S. Dalton, and T. P. Loughran Jr Dysregulation of CD95/CD95 Ligand-Apoptotic Pathway in CD3+ Large Granular Lymphocyte Leukemia Blood, December 15, 1998; 92(12): 4771 - 4777. [Abstract] [Full Text] [PDF]