Identification and characterization of the specific murine NK cell subset supporting graft-versus-leukemia- and reducing graft-versus-host-effects

Meinhardt K, Kroeger I, Bauer R, Ganss F, Ovsiy I, Rothamer J, Büttner M, Atreya I, Waldner M, Bittrich M, Lehmann C, Rieger MA, Beilhack A, Zeiser R, Edinger M, Dudziak D, Mackensen A, Rehli M, Evelyn U (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 4

Pages Range: e981483

Journal Issue: 1

DOI: 10.4161/2162402X.2014.981483

Abstract

Clinical studies investigating the impact of natural killer (NK) cells in allogeneic hematopoietic stem cell transplantation settings have yielded promising results. However, NK cells are a functionally and phenotypically heterogeneous population. Therefore, we addressed the functional relevance of specific NK cell subsets distinguished by expression of CD117, CD27 and CD11b surface markers in graft-versus-leukemia (GVL)-reaction and graft-versus-host-disease (GVHD). Our results clearly demonstrate that the subset of c-Kit(-)CD27(-)CD11b(+) NK cells expressed multiple cytotoxic pathway genes and provided optimal graft-versus-leukemia-effects, while significantly reducing T cell proliferation induced by allogeneic dendritic cells. Furthermore, these NK cells migrated to inflamed intestinal tissues where graft-versus-host-colitis was efficiently mitigated. For the first time, we identified the c-Kit(-)CD27(-)CD11b(+) NK cell population as the specific effector NK cell subset capable of significantly diminishing GVHD in fully mismatched bone marrow transplantation settings. In conclusion, the subset of c-Kit(-)CD27(-)CD11b(+) NK cells not only supports GVL, but also plays a unique role in the protection against GVHD by migrating to the peripheral GVHD target organs where they exert efficient immunoregulatory activities. These new insights demonstrate the importance of selecting the optimal NK cell subset for cellular immunotherapy following allogeneic hematopoietic stem cell transplantation.

Authors with CRIS profile

Involved external institutions

Goethe-Universität Frankfurt am Main Germany (DE) Albert-Ludwigs-Universität Freiburg Germany (DE) Universitätsklinikum Regensburg Germany (DE)

How to cite

APA:

Meinhardt, K., Kroeger, I., Bauer, R., Ganss, F., Ovsiy, I., Rothamer, J.,... Evelyn, U. (2015). Identification and characterization of the specific murine NK cell subset supporting graft-versus-leukemia- and reducing graft-versus-host-effects. OncoImmunology, 4(1), e981483. https://dx.doi.org/10.4161/2162402X.2014.981483

MLA:

Meinhardt, Kathrin, et al. "Identification and characterization of the specific murine NK cell subset supporting graft-versus-leukemia- and reducing graft-versus-host-effects." OncoImmunology 4.1 (2015): e981483.

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