title: Mouse natural killer subsets defined by their target specificity and their ability to be separately rendered unresponsive in vivo.
abstract: NK cells from F1(AxB) hybrid mice are known to reject bone marrow grafts from either parent A or parent B (hybrid resistance). Using cold target competition in an in vitro hybrid resistance assay, we demonstrate in this work that parent A and parent B are killed by different NK subsets. As confirmation of the existence of these subsets, and to determine whether they undergo a selection/education process during NK cell ontogeny, we constructed bone marrow chimeras in which NK1.1-depleted bone marrow cells from F1 mice were allowed to mature in the microenvironment of either parent A or parent B. These F1-reconstituted chimeras were shown to have normal NK cell numbers and lytic ability in terms of YAC-1 killing and Ab-mediated redirected lysis. Using a three-color flow cytometry analysis in an in vivo hybrid resistance assay, we found that A targets, but not B targets, were less effectively removed by the F1 NK cells that develop in an A recipient (F1-->A chimeras) than in normal F1 or F1-->F1 chimeric mice. IL-2-activated killer cultures of cells from these chimeras, however, did not show a significant difference in the anti-parent killing response in an in vitro assay. These results suggest that NK cells exist in subsets and that self-reactive NK subsets can be rendered unresponsive by radioresistant host element(s). However, this unresponsiveness can be broken when the NK cells are removed from the in vivo environment.
authors.affiliation: Ontario Cancer Institute, Department of Medical Biophysics, University of Toronto, Canada.
authors.forename: S K
authors.initials: SK
authors.lastname: Kung
authors.forename: R G
authors.initials: RG
authors.lastname: Miller
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000235:genetics; D007694:Killer Cells, Natural / Q000145:classification* / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology