title: UV irradiation of immunized mice induces type 1 regulatory T cells that suppress tumor antigen specific cytotoxic T lymphocyte responses.
abstract: We previously showed that exposure to UV radiation after immunization suppresses Th1 and Th2 immune responses, leading to impaired Ab and allo-immune responses, but the impact of UV radiation after immunization on anti-tumor immune responses mediated by tumor-specific CD8(+) T cell responses remains less clear. Furthermore, the exact phenotypic and functional characteristics of regulatory T cell population responsible for the UV-induced immunosuppression still remain elusive. Using the MBL-2 lymphoma cell line engineered to express OVA as a surrogate tumor Ag, here we demonstrate that UV irradiation after tumor Ag-immunization suppresses the anti-tumor immune response in a manner dependent on the immunizing Ag. This suppression was mediated by interleukin (IL)-10 released from CD4(+) CD25(+) T cells, by which impaired the induction of cytotoxic T lymphocytes (CTL) able to kill Ag-expressing tumor cells. In addition, we generated a panel of T cell clones from UV-irradiated and non-irradiated mice, and all of the clones derived from UV-irradiated mice had a Tr1-type regulatory T cell phenotype with expression of IL-10 and c-Maf, but not Foxp3. These Tr1-type regulatory T cell clones suppressed tumor rejection in vivo as well as Th cell activation in vitro in an IL-10 dependent manner. Given that suppression of Ag-specific CTL responses can be induced in Ag-sensitized mice by UV irradiation, our results may imply that exposure to UV radiation during premalignant stage induces tumor-Ag specific Tr1 cells that mediate tumor-Ag specific immune suppression resulting in the promotion of tumor progression.
authors.affiliation: Department of Cellular and Molecular Immunology, Mie Graduate School of Medicine, Tsu, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
authors.forename: Linan
authors.initials: L
authors.lastname: Wang
authors.forename: Suguru
authors.initials: S
authors.lastname: Ogura
authors.forename: Mie
authors.initials: M
authors.lastname: Torii
authors.forename: Makoto
authors.initials: M
authors.lastname: Kurachi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kakimi
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
authors.forename: Kagemasa
authors.initials: K
authors.lastname: Kuribayashi
authors.forename: Takuma
authors.initials: T
authors.lastname: Kato
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000528:radiation effects; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000528:radiation effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007108:Immune Tolerance; D007114:Immunization; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000378:metabolism*; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D051257:Proto-Oncogene Proteins c-maf / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000528:radiation effects*; D018417:Th1 Cells / Q000276:immunology* / Q000528:radiation effects; D018418:Th2 Cells / Q000276:immunology* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: C495608:Maf protein, mouse; D051257:Proto-Oncogene Proteins c-maf; D012333:RNA, Messenger; D016753:Interleukin-10; D010047:Ovalbumin