title: Interleukin-2 augmented activation of tumor associated macrophage plays the main role in MHC class I in vivo induction in tumor cells that are MHC negative in vitro.
abstract: The contribution of tumor associated macrophage (TAM) to the induction of major histocompatibility complex (MHC) class I expression in vivo has not been reported precisely. In this study, we utilized Interleukin-2 (IL-2) cDNA-introduced B16 melanoma cells (B16/IL-2) and vehicle-alone control cells (B16/mock) to examine whether TAM could contribute to the induction of MHC class I on B16 cells in vivo. Interestingly, although B16/mock and B16/IL-2 did not express MHC class I in vitro, MHC class I was strongly expressed in vivo in B16/IL-2 in comparison to B16/mock. Although in vivo treatment of anti-NK1.1 antibody abolished MHC expression in B16/mock in vivo, the same treatment did not influence MHC expression in B16/IL-2. Interestingly, both anti-asialo GM1 and anti-CD11b treatment strongly decreased MHC expression in B16/IL-2. TAM expressed both asialo GM1 and CD11b antigen, and TAM recovered from B16/IL-2 produced interferon gamma (IFNgamma) 6 times more than that from B16/mock. In addition, TAM recovered from B16/IL-2 secreted 33.64 times more IFNgamma in response to in vitro administration of IL-2. Therefore, we checked whether or not IL-2 could influence the expression of IL-2 receptors. TAM recovered from IL-2 expressed middle affinity receptor of IL-2 (CD122 and CD132) while that from B16/mock expressed low affinity receptor (CD25 and CD132). Finally, we observed that B16 cells became apoptotic with IFNgamma treatment in vitro. These results suggested that IL-2 augmented activation of TAM would play the main role in induction of the MHC class I molecule through secretion of IFNgamma, and would contribute to the IFNgamma-mediated apoptosis induction in tumor cells.
authors.affiliation: Department of Immunopathology, Gifu University Graduate School of Medicine, Yanagido, Gifu, Japan.
authors.forename: Guan-Feng
authors.initials: GF
authors.lastname: Ouyang
authors.forename: Masanao
authors.initials: M
authors.lastname: Saio
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Suwa
authors.forename: Hisashi
authors.initials: H
authors.lastname: Imai
authors.forename: Jiro
authors.initials: J
authors.lastname: Nakagawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nonaka
authors.forename: Naoki
authors.initials: N
authors.lastname: Umemura
authors.forename: Mika
authors.initials: M
authors.lastname: Kijima
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takami
mesh_terms: D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2