Involvement of MHC class I molecule and ICAM-1 in the enhancement of adhesion and cytotoxic susceptibility to immune effector cells of tumor cells transfected with the interleukin (IL)-2, IL-4 or IL-6 gene.
To investigate the molecular and cellular mechanisms involved in the reduced tumorigenicity and increased immunogenicity of interleukin-2 (IL-2)-, IL-4- or IL-6-gene-transfected B16 melanoma vaccine, we have analyzed the functional and phenotypic properties of these genetically engineered melanoma cells in the present study. The cytokine-gene-transfected B16 melanoma cells showed stronger adhesion to the lymphokine-activated killer (LAK) cells or cytotoxic T lymphocytes (CTL), and higher sensitivity to cytotoxicity of LAK cells or CTL. Using fluorescence-activated cell sorting analysis, we found that both MHC class I and ICAM-1 expression were increased after IL-2, IL-4 or IL-6 gene transfection. The increased level of MHC class I and ICAM-1 expression seems to be responsible for the high sensitivity of these gene-transfected B16 cells to LAK or CTL cytotoxicity because anti-(MHC class I) or anti-ICAM-1 mAb could inhibit the adhesion and cytotoxicity increment simultaneously. The CTL induction was partly inhibited by anti-ICAM-1 mAb and was completely blocked by anti-MHC class I mAb. These results suggested that the decreased tumorigenicity of IL-2-, IL- 4-, and IL-6-gene-transfected B16 melanoma cells may be partly due to the increased sensitivity to effector cell cytotoxicity mediated by increased expression of ICAM-1 or MHC class I molecules on the tumor cell surface after cytokine gene transfection.
Cao
X
X
Department of Immunology, Second Military Medical University, Shanghai, PR China.
Chen
G
G
He
L
L
Zhang
W
W
Yu
Y
Y
Wang
J
J
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D015979:Killer Cells, Lymphokine-Activated / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D007376:Interleukin-2; D015850:Interleukin-6; D007378:Interleukins; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4