Mouse lymphoblasts lose their immunogenicity and susceptibility to specific cytotoxic T lymphocyte lysis during maintenance in culture.
This study was undertaken to search for possible mechanisms by which T-cell lines become non-immunogenic and refractory to cellular-mediated lysis during culture. We demonstrate that mouse lymphoblasts (LB) lost their susceptibility to specific cytotoxic T lymphocyte (CTL)-mediated lysis following culture for more than 5 days in the presence interleukin-2 (IL-2), IL-7 but not IL-4. In contrast, the cultured lymphoblasts (CLB) were efficiently lysed by specific antibody and C' and by CTL in the presence of concanavalin A. In addition, CLB did not inhibit cytotoxicity against LB in a cold target competition assay, indicating that CLB and LB differ in the expression of certain surface molecules. Indeed, a significantly lower expression of H-2D class I antigen, the Fas antigen and the adhesion molecules intracelluar adhesion molecule-1 (ICAM-1) and very late activation antigen-4 (VLA-4) was observed on the CLB surface. Consequently, CLB could not form conjugates with specific CTL, a prerequisite for CTL-mediated lysis. In addition, there was a marked decrease in CLB immunogenicity: the cultured cells were unable to stimulate allogeneic spleen cells in mixed lymphocyte culture nor could they induce a cytotoxic response following their injection into allogeneic mice. The reduced immunogenicity enabled the prolonged survival of active CLB in an allogeneic host. We suggest that the extended survival in an allogeneic tumour-bearing host of cultured, hence weakly immunogenic, anti-tumour CTL, will enable them the in vivo implementation of their anti-tumour activity.
Leshem
B
B
The Lautenberg Centre for General and Tumour Immunology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Brass
D
D
D000818:Animals; D001667:Binding, Competitive; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007108:Immune Tolerance; D007378:Interleukins / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D007378:Interleukins; D019014:fas Receptor