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Functional NK cell repertoires are maintained through IL-2Rα and fas ligand

Journal of Immunology, ISSN: 1550-6606, Vol: 192, Issue: 8, Page: 3889-3897
2014
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Article Description

Acquisition of a functional NK cell repertoire, known as education or licensing, is a complex process mediated through inhibitory receptors that recognize self.We found that NK cells containing self-killer Ig-like receptors for cognate HLA ligand in vivo were less susceptible to apoptosis. In vitro IL-15 withdrawal showed that uneducated NK cells upregulated Bim and Fas. Conversely, educated NK cells upregulated Fas ligand (FasL) under these conditions. Induction of cell death and Bim expression on uneducated cells correlated with increased IL-2Rα expression. Overexpression and knockdown studies showed that higher IL-2Rα limits NK cell survival in a novel manner that is independent from the role of IL-2 in activation-induced cell death. To study the role of FasL in induction of IL-2Rα NK cell death, a coculture assay with FasL-blocking Abs was used. IL-15 withdrawal led to FasL-dependent killing of IL-2Rα NK cells by more educated IL-2Rα NK cells. Finally, CMV reactivation induces a potent long-lasting population of licensed NK cells with enhanced survival. These findings show that education-dependent NK cell survival advantages and killing of uneducated NK cells result in the maintenance of a functional repertoire, which may be manipulated to exploit NK cells for cancer immunotherapy. Copyright © 2014 by The American Association of Immunologists, Inc.

Bibliographic Details

Felices, Martin; Lenvik, Todd R; Ankarlo, Dave E M; Foley, Bree; Curtsinger, Julie; Luo, Xianghua; Blazar, Bruce R; Anderson, Stephen K; Miller, Jeffrey S

Oxford University Press (OUP)

Medicine; Immunology and Microbiology

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