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Cell Rep. 2014 Jun 26;7(6):1809-14. doi: 10.1016/j.celrep.2014.05.011. Epub 2014 May 29.

NK cell receptor NKp46 regulates graft-versus-host disease.

Author information

1
The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel.
2
Hematology Division, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
3
The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem 91120, Israel. Electronic address: oferm@ekmd.huji.ac.il.

Abstract

Hematopoietic stem cell transplantation (HSCT) is often the only curative treatment for a wide variety of hematologic malignancies. Donor selection in these diseases is crucial, given that transplanted cells can mediate not only the desired graft-versus-leukemia effect but also graft-versus-host disease (GVHD). Here, we demonstrate that in the absence of NKp46, a major killer receptor expressed by human and mouse natural killer (NK) cells, GVHD is greatly exacerbated, resulting in rapid mortality of the transplanted animals because of infection with commensal bacteria. Furthermore, we demonstrate that the exacerbated GVHD is the result of an altered ability of immune cells to respond to stimulation by immature dendritic cells. Because high and low expression of NKp46 on NK cells is observed in different individuals, our data indicate that choosing NKp46-high donors for the treatment of different hematologic malignancies might lead to better tumor eradication while minimizing GVHD.

PMID:
24882008
PMCID:
PMC4074424
DOI:
10.1016/j.celrep.2014.05.011
[Indexed for MEDLINE]
Free PMC Article

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