NK sensitivity and lung clearance of MHC-class-I-deficient cells within a heterogeneous fibrosarcoma.
The present study examines clonal variations in NK sensitivity in a methylcholanthrene-induced fibrosarcoma. Previous studies of clones from this tumor have shown considerable heterogeneity in H-2 expression, and an association between deleted or low levels of class-I products and increased tumorigenicity after subcutaneous implantation in immunocompetent syngeneic mice. Here, fibrosarcoma clones with no or low expression of MHC-class-I products were found to be sensitive to NK-mediated lysis, while clones with high levels of MHC-class-I expression were relatively resistant. One H-2+ (G2) and one H-2- (B9) clone were chosen for more detailed studies. Cold-target competition assays and conjugate cytotoxicity assays in agarose showed that splenic effector cells bound equally well to the H-2+ and H-2- tumor clone, although only the latter was sensitive to NK cell lysis. Treatment with 50 U/ml of rIFN-gamma for 48 hr increased the levels of H-2 expression and made both clones more resistant to NK-mediated lysis. In vivo studies with radiolabelled tumor cells showed that cells from the H-2+ clone survived better than cells from the H-2- clone in the pulmonary capillary bed after i.v. inoculation. This difference disappeared in mice treated with anti-asialo GM1 serum, known to deplete NK cell activity.
Algarra
I
I
Dept. of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
Ohlén
C
C
Perez
M
M
Ljunggren
H G
HG
Klein
G
G
Garrido
F
F
Kärre
K
K
D000818:Animals; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D005354:Fibrosarcoma / Q000139:chemically induced / Q000276:immunology*; D005677:G(M1) Ganglioside; D005805:Genes, MHC Class I / Q000187:drug effects / Q000502:physiology*; D006028:Glycosphingolipids / Q000276:immunology; D006183:H-2 Antigens / Q000032:analysis; D007106:Immune Sera / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D006028:Glycosphingolipids; D006183:H-2 Antigens; D007106:Immune Sera; D005677:G(M1) Ganglioside; D008748:Methylcholanthrene; C018835:asialo GM1 ganglioside; D007371:Interferon-gamma