Class I-deficient hemopoietic cells and nonhemopoietic cells dominantly induce unresponsiveness of natural killer cells to class I-deficient bone marrow cell grafts.
NK cells in normal mice reject bone marrow transplants from class I-deficient mice. In contrast, class I-deficient mice do not reject autologous cells, suggesting that NK cell tolerance is acquired. We employed fetal liver irradiation chimeras to assess two potential mechanisms that could account for the tolerance of NK cells in class I-deficient mice to class I-deficient cells: 1) a positive model, in which recognition of class I+ cells molecules by NK cells is necessary to induce functional NK cell maturation; and 2) a negative model, in which interactions of NK cells with class I-deficient cells induce tolerance. In class I+ chimeras reconstituted with mixtures of class I+ and class I-deficient fetal liver cells, the rejection of class I-deficient bone marrow cell grafts was significantly impaired, supporting the negative model. We further addressed whether nonhemopoietic cells are also able to induce NK cell tolerance. Class I- mice reconstituted with class I+ fetal liver cells were tolerant of class I-deficient cells, favoring this idea. Furthermore, class I-deficient mice reconstituted with a mixture of class I-deficient and class I+ fetal liver cells were more tolerant to class I-deficient cells than were class I+ mice reconstituted with the same fetal liver cell mixture. These results suggest that maximal tolerance induction requires the presence of class I-deficient nonhemopoietic cells.
Wu
M F
MF
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Raulet
D H
DH
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D003433:Crosses, Genetic; D005260:Female; D005799:Genes, Dominant / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D007108:Immune Tolerance / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011828:Radiation Chimera / Q000276:immunology; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin