Interleukin-10 inhibited the expression of tumor antigens and major histocompatibility complex antigen on EJ-ras oncogene transformants.
Interleukin-10 (IL-10), a novel inhibitory cytokine, is one of Th-2 (T helper) cytokine. It inhibits mixed lymphocyte reaction, and the production of inflammatory cytokine and monokine downregulates major histocompatibility complex antigen (MHC) class II antigen expression. However, the effect of IL-10 on tumor cells is not known. Therefore, the mechanism of tumor tolerance induced by IL-10 was investigated. (WKA rat fetus-derived fibroblast) (WFB) and W14 and W31 (EJ-ras oncogene transformants of WFB) were cultured with recombinant human (rh)IL-10 (0, 10, 50, 100 ng/ml). FACS analysis was performed using the following monoclonal antibodies: anti-rat MHC class I monoclonal antibody; and monoclonal antibody 109 (anti-natural killer [NK] target molecule on W14). Monoclonal antibody (mAb) 109-defined antigens were newly expressed during the transforming process by EJ-ras oncogene transfection to WFB. In addition, the effects of rhIL-10 on the ability of proliferation and susceptibility to NK cells were assessed. The cultivation with rhIL-10 resulted in a dose-dependent decrease in the expressions of MHC class I antigen and monoclonal antibody 109-defined antigen. The proliferation and susceptibility to NK cells of W14 were inhibited. These data demonstrated a possibility that IL-10 could induce tumor tolerance to host immunity by inhibiting the expression of tumor-associated antigens and MHC class I.
Tsuruma
T
T
Department of Surgery, Sapporo Medical University, Japan.
Yagihashi
A
A
Torigoe
T
T
Okada
Y
Y
Sato
N
N
Kikuchi
K
K
Hirata
K
K
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D005802:Genes, MHC Class II / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D011905:Genes, ras / Q000235:genetics / Q000276:immunology; D006087:Graft vs Host Reaction / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D016753:Interleukin-10