Host H-2 genotype regulates the metastatic ability of H-2-associated variants of B16 melanoma: defense systems screening for absence of self H-2 components by natural killer cells and host-associated homing barrier.
The mechanisms of host H-2-associated resistance against metastasis of tumor cells were evaluated in relation to the H-2 phenotype of tumor cells. We used H-2 heterozygous H-2a/b and H-2d/b, and H-2 homozygous H-2b/b hosts, and H-2-associated variant lines of B16 cells (H-2b+, H-2b-). In H-2b/b hosts, H-2+ cells were highly metastatic in vivo, and were resistant to host NK effectors in vitro. Therefore, H-2a/b and H-2d/b hosts showed resistance to metastasis of H-2+ cells and their effectors showed killing activity to these cells in vitro. Though the host resistance was reduced by anti-asialo GM1 serum treatment, these hosts continued to demonstrate a considerable resistance against early survival and metastasis of the B16 cells. To evaluate this natural resistance, aside from the NK system, radiation bone marrow chimeras of F1-parental combinations were used. The data suggest that host MHC-associated resistance involves not only the NK defense system but also the host environmental resistance. Both exert resistance by recognizing the H-2 mismatch in relation to the host.
Kawano
Y
Y
Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Taniguchi
K
K
Kärre
K
K
Toshitani
A
A
Nomoto
K
K
D000818:Animals; D002470:Cell Survival; D002678:Chimera; D005838:Genotype; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D006579:Heterozygote; D007157:Immunologic Surveillance; D007694:Killer Cells, Natural / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009362:Neoplasm Metastasis
D006183:H-2 Antigens