NK sensitivity and lung clearance of MHC-class-I-deficient cells within a heterogeneous fibrosarcoma.

Abstract

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.

• Authors: I Algarra, C Ohlén, M Perez, H G Ljunggren, G Klein, F Garrido, K Kärre
• Journal: International journal of cancer (Int J Cancer) Vol. 44 Issue 4 Pg. 675-80 (Oct 15 1989) ISSN: 0020-7136 [Print] United States
• PMID: 2507453 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Glycosphingolipids
• H-2 Antigens
• Immune Sera
• G(M1) Ganglioside
• Methylcholanthrene
• asialo GM1 ganglioside
• Interferon-gamma

Topics

• Animals
• Cell Line
• Cytotoxicity Tests, Immunologic
• Fibrosarcoma (chemically induced, immunology)
• G(M1) Ganglioside
• Genes, MHC Class I (drug effects, physiology)
• Glycosphingolipids (immunology)
• H-2 Antigens (analysis)
• Immune Sera (pharmacology)
• Interferon-gamma (pharmacology)
• Killer Cells, Natural (drug effects, immunology)
• Lung (drug effects, immunology)
• Methylcholanthrene
• Mice
• Mice, Inbred BALB C
• Tumor Cells, Cultured
• Tumor Stem Cell Assay