Persisting NK cell alloreactivity in the presence of long-term stable hematopoietic chimerism.
OBJECTIVE
Like other lymphocytes, natural killer (NK) cells need to develop tolerance toward self. In the last decade, major progress has been made in understanding the molecular mechanisms behind this phenomenon. Yet the cellular mechanisms regulating the education of NK cells remain poorly understood. This study aimed to unravel the cellular mechanisms regulating NK-cell tolerance in the context of alloreactivity.


METHODS
Using the classical hybrid resistance model and an in vivo cytotoxicity assay, we examined host NK-cell alloreactivity against donor hematopoietic cells in the presence of long-term stable chimerism.


RESULTS
We demonstrate persisting host NK-cell alloreactivity against donor hematopoietic cells, despite the presence of long-term stable chimerism. This NK-cell alloreactivity decreases with increasing levels of parental chimerism.


CONCLUSIONS
Our results indicate that long-term mixed hematopoietic chimerism does not necessarily imply the induction of full NK-cell nonresponsiveness. NK-cell nonresponsiveness is, therefore, not an absolute phenomenon, but represents a dynamic process, balancing NK-cell alloreactivity against the size of the transplanted allogeneic stem cell pool.
Westerhuis
Geert
G
Department of Immunohematology, Leiden University Medical Center, Leiden, The Netherlands.
Maas
Wendy G E
WG
Toes
René E M
RE
Fibbe
Willem E
WE
D000818:Animals; D016026:Bone Marrow Transplantation; D003602:Cytotoxicity, Immunologic; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017634:Self Tolerance / Q000276:immunology; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000276:immunology*