NK cell education after allogeneic transplantation: dissociation between recovery of cytokine-producing and cytotoxic functions

Bree Foley, Sarah Cooley, Michael R Verneris, Julie Curtsinger, Xianghua Luo, Edmund K Waller, Daniel J Weisdorf, Jeffrey S Miller

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Natural killer (NK) cells mediate GVL effects after allogeneic hematopoietic cell transplantation (allo-HCT) by the production of inflammatory cytokines and by direct target lysis. The acquisition of both functions was presumed to be developmentally linked, but this linkage remained unstudied after allo-HCT. We tested the cytokine production and degranulation of reconstituting NK cells after adult unrelated donor or umbilical cord blood grafting. Recipients of T cell-depleted transplants, receiving no immune suppression, showed diminished NK cell degranulation. In contrast, degranulation was normal or increased after T-cell replete transplants given with immune suppression. Strikingly, target cell-induced IFNγ production was markedly diminished in all transplant settings, especially with T cell-depleted or naive T cell-containing umbilical cord blood grafts, suggesting a role for T cells in NK education. Although degranulation was similar in the KIR(+) and KIR(-) populations that coexpressed NKG2A, target cell-induced IFNγ production was limited to the subset of NK cells expressing KIR inhibited by self-ligands. Thus, cytokine production and cytotoxic function do not consistently coexist in NK cells reconstituting after allo-HCT. Exposure to IL-15 rapidly increased target-inducible IFNγ production, indicative of IL-15's potential as a therapeutic tool to enhance NK cell function to protect against infection and relapse after allo-HCT.

Original languageEnglish
Pages (from-to)2784-92
Number of pages9
JournalBlood
Volume118
Issue number10
DOIs
Publication statusPublished - 8 Sep 2011
Externally publishedYes

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