Meinhardt, Kathrin and Kroeger, Irena and Bauer, Ruth and Ganss, Franziska and Ovsiy, Ilja and Rothamer, Johanna and Buettner, Maike and Atreya, Imke and Waldner, Maximilian and Bittrich, Max and Lehmann, Christian H. K. and Rieger, Michael A. and Beilhack, Andreas and Zeiser, Robert and Edinger, Matthias and Dudziak, Diana and Mackensen, Andreas and Rehli, Michael and Ullrich, Evelyn (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. ISSN 2162-402X,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NATURAL-KILLER-CELLS; BONE-MARROW-TRANSPLANTATION; KIR LIGAND INCOMPATIBILITY; ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC TRANSPLANTS; PHASE-II; T-CELLS; EXPANSION; CANCER; IMMUNOTHERAPY; GVHD; GVL; NK cells; stem cell transplantation; tumor immunology |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Aug 2019 12:51 |
| Last Modified: | 01 Aug 2019 12:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6301 |
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