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

被引:111
作者
Foley, Bree
Cooley, Sarah
Verneris, Michael R.
Curtsinger, Julie
Luo, Xianghua [2 ,3 ]
Waller, Edmund K. [4 ]
Weisdorf, Daniel J.
Miller, Jeffrey S. [1 ]
机构
[1] Univ Minnesota, Div Hematol Oncol & Transplantat, Ctr Canc, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Div Biostat, Sch Publ Hlth, Minneapolis, MN 55455 USA
[3] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA
[4] Emory Univ, Winship Canc Ctr, Bone Marrow & Stem Cell Transplant Ctr, Atlanta, GA 30322 USA
基金
美国国家卫生研究院;
关键词
NATURAL-KILLER-CELLS; CLASS-I MOLECULES; MHC CLASS-I; UNRELATED DONOR TRANSPLANTATION; EXPRESSING INHIBITORY KIR; SELF-TOLERANCE; MISSING SELF; T-CELLS; RECEPTORS; RECONSTITUTION;
D O I
10.1182/blood-2011-04-347070
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 IFN gamma 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 IFN gamma 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 IFN gamma 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. (Blood. 2011;118(10):2784-2792)
引用
收藏
页码:2784 / 2792
页数:9
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