title: Afferent and efferent cellular interactions in natural resistance directed against MHC class I deficient tumor grafts.
abstract: H-2-deficient variants, selected from the murine lymphoma RBL-5, were recently shown to be less tumorigenic in syngeneic mice compared with the corresponding H-2-positive wild-type cell line. The present study focused on the detailed cellular interactions leading to the specific rejection of H-2-deficient cells in vivo. In vivo experiments with mixed tumor inocula, measuring either tumor outgrowth or rapid elimination, showed that the presence of H-2-positive lymphoma cells did not suppress the rejection of H-2-deficient cells. Conversely, H-2-deficient cells did not activate a rejection of H-2-positive cells. H-2-deficient cells were selectively eliminated even when they were present in a 10-fold excess compared with the H-2-positive lymphoma cells in the same inoculum. In vitro, H-2-deficient cells were more sensitive to killing by spleen cells from mice treated with interferon or natural killer-inducing agents. The presence of cold H-2-deficient cells did not activate the killing of H-2-positive cells, and H-2-positive cells did not inhibit killing of H-2-deficient cells. Such mixing experiments revealed a more efficient cold target inhibition by the H-2-deficient cells, although no difference was seen between these and the H-2-positive wild-type cells in target binding assays. When Thy-1.2+, nylon wool adherent or phagocytic populations were removed from normal spleen effectors, the difference in spontaneous cell-mediated cytotoxicity between the H-2-deficient and the H-2-positive cells persisted. This result was also obtained when spleen cell effectors from nude mice or asialo GM1+ effectors, positively enriched by fluorescence-activated cell sorter, were used. The results show that the selectivity in the rejection of H-2-deficient cells was not determined in the afferent arm alone. The present data fit with a previously proposed model where natural killer cells would bind equally well to both major histocompatibility complex class I negative and class I positive target cells, but only the latter would be able to present a postbinding inhibitory signal allowing them to escape killing which results in outgrowth in vivo and poor cold target competition in vitro.
authors.affiliation: Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
authors.forename: H G
authors.initials: HG
authors.lastname: Ljunggren
authors.forename: C
authors.initials: C
authors.lastname: Ohlén
authors.forename: P
authors.initials: P
authors.lastname: Höglund
authors.forename: T
authors.initials: T
authors.lastname: Yamasaki
authors.forename: G
authors.initials: G
authors.lastname: Klein
authors.forename: K
authors.initials: K
authors.lastname: Kärre
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002450:Cell Communication; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013154:Spleen / Q000166:cytology; D014407:Tumor Cells, Cultured
chemical_list: D006183:H-2 Antigens