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

✍ Scribed by Ignacio Algarra; Claes Ohlén; Matias Perez; Hans-Gustaf Ljunggren; George Klein; Federico Garrido; Klas Karre

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: French
• Weight: 598 KB
• Volume: 44
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910440420

✦ Synopsis

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-class4 products were found to be sensitive to NK-mediated lysis, while clones with high levels of MHC-class4 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 rlFN-y 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 GM, serum, known to deplete NK cell activity.