Format

Send to

Choose Destination
Oncoimmunology. 2015 Feb 3;4(1):e981483. eCollection 2015 Jan.

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

Author information

1
Department of Internal Medicine 5; Hematology and Oncology; Friedrich-Alexander Universität Erlangen-Nürnberg; University Hospital Erlangen ; Erlangen, Germany ; Childrens Hospital; Department of Pediatric Hematology and Oncology; Johann Wolfgang Goethe University ; Frankfurt, Germany ; LOEWE Center for Cell and Gene Therapy; Johann Wolfgang Goethe University ; Frankfurt, Germany.
2
Department of Internal Medicine 5; Hematology and Oncology; Friedrich-Alexander Universität Erlangen-Nürnberg; University Hospital Erlangen ; Erlangen, Germany.
3
Childrens Hospital; Department of Pediatric Hematology and Oncology; Johann Wolfgang Goethe University ; Frankfurt, Germany ; LOEWE Center for Cell and Gene Therapy; Johann Wolfgang Goethe University ; Frankfurt, Germany.
4
Department of Nephropathology; Friedrich-Alexander Universität Erlangen-Nürnberg; University Hospital Erlangen ; Erlangen, Germany.
5
Department of Internal Medicine 1; Friedrich-Alexander Universität Erlangen-Nürnberg; University Hospital Erlangen ; Erlangen, Germany.
6
Department of Dermatology; Laboratory of Dendritic Cell Biology; Friedrich-Alexander Universität Erlangen-Nürnberg; University Hospital Erlangen ; Erlangen, Germany.
7
LOEWE Center for Cell and Gene Therapy; Johann Wolfgang Goethe University ; Frankfurt, Germany ; Department of Hematology/Oncology; Johann Wolfgang Goethe University ; Frankfurt, Germany.
8
IZKF Research Group for Experimental Stem Cell Transplantation; Department of Medicine II; University Hospital ; Würzburg, Germany.
9
Division of Hematology and Oncology; Department of Medicine; Freiburg University Medical Center; Albert-Ludwigs-University ; Freiburg, Germany.
10
Department of Internal Medicine 3; University Hospital Regensburg ; Regensburg; Germany ; Regensburg Center for Interventional Immunology (RCI); University Regensburg ; Regensburg, Germany.

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.

KEYWORDS:

BMT, bone marrow transplantation; CD11b+ NK = c-Kit−CD27−CD11b+ NK cells; CD27+ NK = c-Kit−CD27+CD11b− NK cells; DP = c-Kit−CD27+CD11b+ NK cells; GVHD; GVHD, graft-versus-host disease; GVL; GVL, graft-versus-leukemia; HSCT, hematopoietic stem cell transplantation; KIR, killer cell immunoglobulin-like receptor; MLR, mixed lymphocyte reaction; NK cells; NK, natural killer; TBI, total body irradiation; c-Kit+ NK = c-Kit+CD27+CD11b− NK cells; stem cell transplantation; tumor immunology

Supplemental Content

Full text links

Icon for Taylor & Francis Icon for PubMed Central
Loading ...
Support Center