The early expansion of a defective NKG2Apos/CD56dim/CD16neg NK cell subset represents a therapeutic target in haploidentical HSCT
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ABSTRACT: Natural Killer (NK) cells are the first lymphocyte population to reconstitute early after non myelo-ablative and T cell-replete haploidentical hematopoietic stem cell transplantations (h-HSCTs) with post-transplant infusion of cyclophosphamide. The present study characterizes the transient and predominant expansion starting from the 2nd week after h-HSCT of a donor-derived unconventional subset of CD56dim/CD16neg (uCD56dim) NK cells expressing remarkable high levels of NKG2A and low levels of NKp46. Both transcription and phenotypic profiles indicated that uCD56dim NK cells are a distinct NK cell subpopulation with features of late differentiation, yet retaining proliferative capability and functional plasticity to generate conventional CD56bright/CD16pos NK cells in response to IL-15 plus IL-18. uCD56dim NK cells represent by far the largest NK cell subset detectable in the following 7 weeks after h-HSCT and they also express high levels of the activating receptors NKGD and NKp30 as well as of the lytic granules Granzyme-B and Perforin. Nonetheless, uCD56dim NK cells displayed a defective cytotoxicity that could be reversed by blocking the inhibitory receptor CD94/NKG2A. These data open new important perspectives to better understand the ontogenesis/homeostasis of human NK cells and to develop a novel immune-therapeutic approach by targeting the inhibitory NKG2A check point, thus enhancing NK cell alloreactivity early after h-HSCT.
ORGANISM(S): Homo sapiens
PROVIDER: GSE107021 | GEO | 2018/05/17
REPOSITORIES: GEO
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