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International Immunology Advance Access originally published online on November 15, 2007
International Immunology 2008 20(1):57-70; doi:10.1093/intimm/dxm124
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Post-immune UV irradiation induces Tr1-like regulatory T cells that suppress humoral immune responses

Linan Wang1,*, Masaaki Toda1,*, Kanako Saito1,2, Tomohide Hori1,3, Toshihiro Horii4, Hiroshi Shiku5,6, Kagemasa Kuribayashi1 and Takuma Kato1

1 Department of Bioregulation
2 Second Department of Internal Medicine
3 First Department of Surgery, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan
4 Department of Molecular Protozoology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
5 Department of Cancer Vaccine
6 Department of Immuno-Gene Therapy, Mie University Gradate School of Medicine, Tsu, Mie, 514-8507, Japan

Correspondence to: T. Kato; E-mail: katotaku{at}doc.medic.mie-u.ac.jp

It is well documented that UV radiation present in sunlight suppresses immune responses, especially Th1-driven cellular immune responses, resulting in the exacerbation of skin cancer and infectious diseases. However, the effects of UV irradiation on humoral immune responses remain less clearly defined. In addition, the majority of studies documenting immunosuppressive effects of UV irradiation has been demonstrated in animals exposed to UV radiation before immunization. In the present study, therefore, we examined the effects of UV irradiation on humoral immune responses in mice that had been immunized before UV irradiation. Both Th1- and Th2-associated Ig responses were significantly suppressed by UV irradiation given 7 days after immunization in an antigen-specific manner. Adoptive transfer experiments revealed that CD4+ T cells from UV-irradiated mice are responsible for the UV-induced suppression of antibody responses. These CD4+ regulatory T cells suppressed proliferation of conventional CD4+ T cells in vivo and in vitro and contained IL-10-producing cells that did not express Foxp3. Mice depleted of CD25+ cells also exhibited reduced antibody responses by UV irradiation. Finally, we showed that CD4+ T cells from UV-irradiated mice treated with anti-IL-10 mAb failed to suppress antibody responses upon transfer. These results indicate that UV irradiation after immunization suppresses Th1- and Th2-mediated humoral immunity via the generation of Tr1-like regulatory T cells, in the process of which IL-10 appears to be important. Possible detrimental effects of UV irradiation after vaccination are also discussed.

Keywords: antibody response, IL-10, regulatory T cell, UV


* These authors contributed equally to this study.

Transmitting editor: M. Miyasaka

Received 21 August 2007, accepted 17 October 2007.


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