Differential Role of Hematopoietic and Nonhematopoietic Cell Types in the Regulation of NK Cell Tolerance and Responsiveness.

Autor:	Shifrin NT; Department of Molecular and Cell Biology, Division of Immunology, University of California at Berkeley, Berkeley, CA 94720, USA., Kissiov DU; Department of Molecular and Cell Biology, Division of Immunology, University of California at Berkeley, Berkeley, CA 94720, USA., Ardolino M; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada and Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada., Joncker NT; Department of Molecular and Cell Biology, Division of Immunology, University of California at Berkeley, Berkeley, CA 94720, USA., Raulet DH; Department of Molecular and Cell Biology, Division of Immunology, University of California at Berkeley, Berkeley, CA 94720, USA.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2016 Nov 15; Vol. 197 (10), pp. 4127-4136. Date of Electronic Publication: 2016 Oct 19.
DOI:	10.4049/jimmunol.1402447
Abstrakt:	Many NK cells express inhibitory receptors that bind self-MHC class I (MHC I) molecules and prevent killing of self-cells, while enabling killing of MHC I-deficient cells. But tolerance also occurs for NK cells that lack inhibitory receptors for self-MHC I, and for all NK cells in MHC I-deficient animals. In both cases, NK cells are unresponsive to MHC I-deficient cells and hyporesponsive when stimulated through activating receptors, suggesting that hyporesponsiveness is responsible for self-tolerance. We generated irradiation chimeras, or carried out adoptive transfers, with wild-type (WT) and/or MHC I-deficient hematopoietic cells in WT or MHC I-deficient C57BL/6 host mice. Unexpectedly, in WT hosts, donor MHC I-deficient hematopoietic cells failed to induce hyporesponsiveness to activating receptor stimulation, but did induce tolerance to MHC I-deficient grafts. Therefore, these two properties of NK cells are separable. Both tolerance and hyporesponsiveness occurred when the host was MHC I deficient. Interestingly, infections of mice or exposure to inflammatory cytokines reversed the tolerance of NK cells that was induced by MHC I-deficient hematopoietic cells, but not the tolerance induced by MHC I-deficient nonhematopoietic cells. These data have implications for successful bone marrow transplantation, and suggest that tolerance induced by hematopoietic cells versus nonhematopoietic cells may be imposed by distinct mechanisms. (Copyright © 2016 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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