Interleukin-10 reduces natural killer sensitivity and downregulates MHC class I expression on H-ras-transformed cells.
We examined the effect of IL-10 on sensitivity to NK-cell-mediated cytotoxicity of the H-ras-induced transformants, W14 and W31. Incubation of cells with recombinant human (rh) IL-10 resulted in a dose-dependent decrease in the expression of MHC class I antigens, but not in the ICAM-1 expression. However, prior incubation of W31 cells with rhIL-10 markedly decreased their susceptibility to cytolysis by rat splenic NK cells. This fact suggested that the IL-10-mediated decrease in MHC class I expression might not dominate the regulation of the NK sensitivity. This was true when rat IL-10 cDNA-introduced W31 cells were used as an endogenous IL-10 producer. The NK sensitivity in vitro of W31T-H, a high IL-10-producer clone, was suppressed downward to the equivalent level of W31 cells pretreated with exogenous rhIL-10. The decreased NK-sensitivity of W31T-H cells was further confirmed by in vivo Winn assay, in which nude mice challenged with W31T-H cells and rat NK cells together developed tumors, whereas nude mice challenged with W31T-L, a minimal-IL-10 producer clone, and NK cells did not. Since neither exogenous nor endogenous IL-10 affected the proliferation of W31 cells, the data indicated that W31T-H cells could evade the NK-cell-mediated immune response in vivo. Taken together, our data reveal a novel mechanism for an IL-10-mediated escape of tumor cells from host immune system by NK cells.
Tsuruma
T
T
Department of Surgery, Sapporo Medical University School of Medicine, Japan.
Yagihashi
A
A
Torigoe
T
T
Sato
N
N
Kikuchi
K
K
Watanabe
N
N
Hirata
K
K
D000818:Animals; D002471:Cell Transformation, Neoplastic; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D005260:Female; D005805:Genes, MHC Class I; D011905:Genes, ras; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000209:etiology / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology
D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins; D016753:Interleukin-10