期刊
BLOOD
卷 129, 期 14, 页码 1940-1946出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2016-08-734285
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资金
- National Institutes of Health National Heart, Lung, and Blood Institute
- European Research Council under the European Union [311335]
- Swedish Research Council
- Norwegian Research Council
- Swedish Foundation for Strategic Research
- Wallenberg Foundation
- Swedish Cancer Foundation
- Swedish Childhood Cancer Foundation
- Stockholm County Council
- Karolinska Institutet Center for Innovative Medicine
- European Research Council (ERC) [311335] Funding Source: European Research Council (ERC)
Natural killer (NK) cells have long been considered short-lived effectors of innate immunity. However, recent animal models and human studies suggest that subsets of NK cells have adaptive features. We investigate clonal relationships of various NK-cell subsets, including the adaptive population, by taking advantage of naturally occurring X-linked somatic PIGA mutations in hematopoietic stem and progenitor cells (HSPCs) from patients with paroxysmal nocturnal hemoglobinuria (PNH). The affected HSPCs and their progeny lack expression of glycosylphosphatidylinositol (GPI) anchors on their cell surface, allowing quantification of PIGA-mutant (GPI-negative) HSPC-derived peripheral blood cell populations. The fraction of GPI-negative cells within the CD56(dim) NK cells was markedly lower than that of neutrophils and the CD56(bright) NK-cell compartments. This discrepancy was most prominent within the adaptive CD56(dim) NK-cell population lacking PLZF expression. The functional properties of these adaptive NK cells were similar in PNH patients and healthy individuals. Our findings support the existence of a long-lived, adaptive NK-cell population maintained independently from GPI(pos)CD56(dim).
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