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Blood. 2011 Jan 20;117(3):764-71. doi: 10.1182/blood-2010-08-264085. Epub 2010 Oct 1.

Killer Ig-like receptor-mediated control of natural killer cell alloreactivity in haploidentical hematopoietic stem cell transplantation.

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  • 1Giannina Gaslini Institute, Genova-Quarto, Italy. lorenzomoretta@ospedale-gaslini.ge.it

Abstract

Natural killer (NK) cells are key members of the innate immune system. In a self-environment, they sense and kill target cells lacking major histocompatibility complex class I molecules and release various cytokines on activation. The discovery of human leukocyte antigen (HLA) class I specific inhibitory receptors (including the allotype-specific killer immunoglobulin-like receptors), and of various activating receptors and their ligands, provided the basis for understanding the molecular mechanism of NK-cell activation and function, mainly resulting from the balance between activating and inhibitory signals. In an allogeneic setting, such as T cell-depleted haploidentical hematopoietic stem cell transplantation, NK cells may express inhibitory killer immunoglobulin-like receptors that are not engaged by any of the HLA class I alleles present on allogeneic cells. Such "alloreactive" NK cells greatly contribute both to eradication of leukemia blasts escaping the preparative regimen and to clearance of residual host dendritic cells and T lymphocytes (thus preventing graft-versus-host disease and graft rejection, respectively). Improved prevention of graft-versus-host disease might be achieved by redirecting to lymph nodes adoptively transferred, alloreactive NK cells by inducing CCR7-uptake in vitro. Recent studies suggested that, after immune-suppressive therapy, alloreactive NK cells from an HLA-haploidentical donor may prevent leukemia recurrence also in patients who have not received allogeneic hematopoietic stem cell transplantation.

PMID:
20889923
[PubMed - indexed for MEDLINE]
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