Enhanced H-2 expression and T-cell-dependent rejection after intracerebral transplantation of the murine lymphoma YAC-1.
The relationship between MHC class I (H-2) expression and tumorigenicity was investigated after intracerebral inoculation of the murine lymphoma YAC-1 and its H-2 negative variant, A.H-2-. YAC-1 was less tumorigenic than A.H-2- in normal as well as NK-depleted syngeneic A/Sn mice. However, in T-cell-depleted syngeneic mice YAC-1 was as tumorigenic as A.H-2-. Following intracerebral growth, the H-2 expression of YAC-1 was markedly enhanced in a similar fashion as after intraperitoneal passage. The A.H-2- variant remained H-2 negative after intracranial passage. The H-2 negative variant cells were not rejected from the brain even when intermixed with wild-type YAC-1 cells prior to intracerebral inoculation, excluding an "innocent bystander" effect. In vitro, the intracerebrally passaged YAC-1 line showed enhanced sensitivity to lysis by H-2 Kk Dd (H-2a) specific CTLs but decreased sensitivity to NK cells. The A.H-2- line was unchanged. Our data suggest that the lack of H-2 molecules may facilitate the growth of antigenic tumor cells in the brain due to escape from T-cell-mediated immunosurveillance. Our data also suggest, in line with other recent findings, that intracerebrally growing tumor cells are sheltered from NK cell-mediated rejection.
Yamasaki
T
T
Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
Ljunggren
H G
HG
Ohlén
C
C
Klein
G
G
Kärre
K
K
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology*; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D006183:H-2 Antigens / Q000032:analysis*; D008223:Lymphoma / Q000276:immunology*; D051379:Mice; D009368:Neoplasm Transplantation; D013601:T-Lymphocytes / Q000276:immunology*
D006183:H-2 Antigens