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Natural resistance against tumors grafted into the brain in association with histocompatibility‐class‐I‐antigen expression
Author(s) -
Yamasaki Toshiki,
Akiyama Yasuhiko,
Fukuda Masako,
Kimura Yoriyoshi,
Moritake Kouzo,
Kikuchi Haruhiko,
Ljunggren HansGustaf,
Kärre Klas,
Klein George
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960729)67:3<365::aid-ijc10>3.0.co;2-7
Subject(s) - major histocompatibility complex , biology , antigen , mhc class i , ctl* , immunology , cell , cytotoxic t cell , microbiology and biotechnology , cancer research , in vitro , cd8 , biochemistry , genetics
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 or in vivo intraperitoneal tumorigenicity between them. Inoculation of Lym + cells into the brain caused up‐regulation 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. © 1996 Wiley‐Liss, Inc.