UV irradiation of immunized mice induces type 1 regulatory T cells that suppress tumor antigen specific cytotoxic T lymphocyte responses

• Published in: International journal of cancer 2011-09, Vol.129 (5), p.1126-1136
• Main Authors: Toda, Masaaki, Wang, Linan, Ogura, Suguru, Torii, Mie, Kurachi, Makoto, Kakimi, Kazuhiro, Nishikawa, Hiroyoshi, Matsushima, Kouji, Shiku, Hiroshi, Kuribayashi, Kagemasa, Kato, Takuma
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antigen (tumor-associated); Biological and medical sciences; Blotting, Western; c-Maf protein; CD25 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - radiation effects; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - radiation effects; Cell activation; CTL; Cytotoxicity; Enzyme-Linked Immunosorbent Assay; Female; Foxp3 protein; Helper cells; IL‐10; Immune Tolerance; Immunization; Immunoregulation; Immunosuppression; Interleukin 10; Interleukin-10 - metabolism; Lymphocyte Activation; Lymphocytes T; Lymphoma; Lymphoma - immunology; Lymphoma - metabolism; Lymphoma - pathology; Medical sciences; Mice; Mice, Inbred C57BL; Ovalbumin; Ovalbumin - administration & dosage; Ovalbumin - immunology; Proto-Oncogene Proteins c-maf - metabolism; regulatory T cell; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - radiation effects; Th1 Cells - immunology; Th1 Cells - radiation effects; Th2 Cells - immunology; Th2 Cells - radiation effects; Tr1; Tumor cell lines; Tumor cells; Tumors; U.V. radiation; Ultraviolet Rays - adverse effects
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.25775

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.