title: Natural resistance against tumors grafted into the brain in association with histocompatibility-class-I-antigen expression.
abstract: The role of MHC-class-I-antigen expression in intracerebral anti-tumor natural resistance was examined using MHC-positive Lym+ and MHC-negative Lym- lymphoma cell lines. Lym+ was sensitive to MHC-class-I-restricted CTL-mediated lysis, while lym- was resistant. Both lines were susceptible to NK-cell-mediated lysis. There was no difference in in vitro growth rate of in vivo intraperitoneal tumorigenicity between them. Inoculation of Lym+ cells into the brain caused upregulation of the intracellular MHC mRNA to the same level as after treatment with interferon-gamma, resulting in an increase in cell-surface MHC expression. Although inoculated Lym- cells also underwent an increase in cytosolic MHC mRNA, the cell-surface MHC expression remained negative. Immunoprecipitation revealed that the terminal glycosylation did not occur normally in Lym-. An in vivo intracerebral tumorigenicity assay, using 2 groups of untreated and NK-cell-depleted syngeneic mice, showed that Lym+ was less tumorigenic than Lym-. In T-cell-depleted mice, however, no difference was detected between them. In addition, when Lym+ and Lym- cells were inoculated into the brain of allogeneic or syngeneic preimmunized mice (immunized with tumor cells), Lym+ was rejected, while Lym- was accepted. When allogeneic mice had received treatment for T-cell depletion before intracerebral inoculation, no rejection was observed in Lym+. On the other hand, Lym- cells, when injected i.p. into NK-depleted mice, had greater killing activity than Lym+ cells, while in T-cell-depleted mice Lym- was less tumorigenic than Lym+. These results suggest that MHC-positive tumor cells grafted into the brain may be rejected by CTL in an MHC-dependent manner, whereas MHC-negative tumor cells can escape from T-cell-mediated immunosurveillance and grow progressively in the brain, due to absence of intracerebral natural resistance mediated by NK cells.
authors.affiliation: Department of Neurosurgery, Shimane Medical University, Izumo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Akiyama
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: Y
authors.initials: Y
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Moritake
authors.forename: H
authors.initials: H
authors.lastname: Kikuchi
authors.forename: H G
authors.initials: HG
authors.lastname: Ljunggren
authors.forename: K
authors.initials: K
authors.lastname: Kärre
authors.forename: G
authors.initials: G
authors.lastname: Klein
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology*; D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D001613:beta 2-Microglobulin / Q000032:analysis
chemical_list: D006183:H-2 Antigens; D001613:beta 2-Microglobulin