Metastatic capacity of cloned T10 sarcoma cells that differ in H-2 expression: inverse relationship to their immunogenic potency.
Clones of the T10 sarcoma, originated in a (H-2b X H-2k)F1 mouse, differ in their metastatic competence, correlated with differences in the expression of antigens of the two parental haplotypes. In fact, the metastatic phenotype is determined by the H-2Dk antigen. Whether the different major histocompatibility complex gene products control the metastatic phenotype via their different immunogenic properties was tested. The involvement of the immune system in controlling the development of metastases was inferred from experiments in which nonmetastatic T10 cloned cells were found to produce both experimental and spontaneous metastases in syngeneic immune-suppressed mice. After the testing of T-cell-mediated immune responses, metastatic T10 cloned cells, which expressed the H-2Db and H-2Dk antigens, were nonimmunogenic in their syngeneic hosts, whereas nonmetastatic T10 cloned cells, which expressed predominantly the H-2Db antigens, evoked a strong T-cell response. H-2Db and H-2Dk antigens expressed on T10 cells appeared to differ in their immunogenicity. This was further supported by the observation that whereas a good antibody response was elicited by H-2Db antigens expressed on T10 cells, only a low anti-H-2Dk antibody was produced. The different T10 cloned cells were not susceptible to natural killer (NK) activity in an in vitro assay, yet in vivo studies suggested the participation of NK activity in controlling T10 metastasis. In animals with depressed NK activity, metastases were generated even by nonmetastatic clones, whereas in animals in which NK activity was elevated, even metastatic clones failed to generate metastases. Both T-cell-mediated immune responses, probably restricted by the H-2D products and NK reactivity, appeared to participate in controlling the development of metastases by T10 cells.
D000818:Animals; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005455:Fluorescent Antibody Technique; D006183:H-2 Antigens / Q000032:analysis* / Q000276:immunology; D007165:Immunosuppression Therapy; D007518:Isoantibodies / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D012513:Sarcoma, Experimental / Q000276:immunology* / Q000556:secondary
D006183:H-2 Antigens; D007518:Isoantibodies