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Prenatal Allospecific NK Cell Tolerance Hinges on Instructive Allorecognition through the Activating Receptor during Development.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2015 Aug 15; Vol. 195 (4), pp. 1506-16. Date of Electronic Publication: 2015 Jul 01. - Publication Year :
- 2015
-
Abstract
- Little is known about how the prenatal interaction between NK cells and alloantigens shapes the developing NK cell repertoire toward tolerance or immunity. Specifically, the effect on NK cell education arising from developmental corecognition of alloantigens by activating and inhibitory receptors with shared specificity is uncharacterized. Using a murine prenatal transplantation model, we examined the manner in which this seemingly conflicting input affects NK cell licensing and repertoire formation in mixed hematopoietic chimeras. We found that prenatal NK cell tolerance arose from the elimination of phenotypically hostile NK cells that express an allospecific activating receptor without coexpressing any allospecific inhibitory receptors. Importantly, the checkpoint for the system appeared to occur centrally within the bone marrow during the final stage of NK cell maturation and hinged on the instructive recognition of allogeneic ligand by the activating receptor rather than through the inhibitory receptor as classically proposed. Residual nondeleted hostile NK cells expressing only the activating receptor exhibited an immature, anergic phenotype, but retained the capacity to upregulate inhibitory receptor expression in peripheral sites. However, the potential for this adaptive change to occur was lost in developmentally mature chimeras. Collectively, these findings illuminate the intrinsic process in which developmental allorecognition through the activating receptor regulates the emergence of durable NK cell tolerance and establishes a new paradigm to fundamentally guide future investigations of prenatal NK cell-allospecific education.<br /> (Copyright © 2015 by The American Association of Immunologists, Inc.)
- Subjects :
- Adoptive Transfer
Animals
Bone Marrow Transplantation
Clonal Anergy genetics
Clonal Anergy immunology
Graft Rejection immunology
H-2 Antigens immunology
Homeostasis
Immunophenotyping
Killer Cells, Natural cytology
Mice
Models, Animal
Phenotype
Transplantation Chimera
Immune Tolerance
Isoantigens immunology
Killer Cells, Natural immunology
Killer Cells, Natural metabolism
Lymphocyte Activation
Receptors, Immunologic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 195
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 26136432
- Full Text :
- https://doi.org/10.4049/jimmunol.1500463