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eISSN: 2329-0358

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Induction of Alloantigen-specific CD4+ T Regulatory Type 1 Cells by Alloantigen Immunization and Ultraviolet-B Irradiation: A Pilot Study in Murine Transplantation Models With Skin and Cardiac Allografts

Tomohide Hori, Kagemasa Kuribayashi, Kanako Saito, Linan Wang, Mie Torii, Shinji Uemoto, Takuma Kato

(Department of Transplant Surgery, Kyoto University Hospital, Kyoto, Japan)

Ann Transplant 2014; 19:519-536

DOI: 10.12659/AOT.890890

Background: The use of ultraviolet (UV)-B irradiation after alloantigen immunization is unknown because previous studies focused on UV-B irradiation before immunization. Here, we investigated immunosuppressive effects induced by UV-B irradiation after immunization, and examined the phenotype of induced regulatory T cells and the possible mechanism of induction.
Material and Methods: B6 mice (H-2^b) were intravenously immunized by splenocytes from CBF1 mice (H-2^b/d). One week after alloantigen immunization, B6 mice received high-dose UV-B irradiation (40 kJ/m^2). Four weeks after UV-B irradiation, proliferation assays (n=4, in each), transplantations with skin or cardiac allografts (n=5, in each), cytokines in mixed lymphocyte culture (n=6, in each), and adoptive transfer of CD4+ T cells to naïve B6 mice (n=5, in each) were performed. Mice were divided into 4 groups: untreated control, immunized control, UV-irradiated control, and an immunized and UV-irradiated group. B6C3F1 mice (H-2^b/k) were used as irrelevant alloantigen with immunization controls. Anti-IL-10 monoclonal antibody was used to block IL-10 before and after UV-B irradiation.
Results: Immune responses against the immunizing antigen were markedly suppressed in immunized and UV-irradiated mice in an alloantigen-specific manner. Surprisingly, CD4+ T cells from immunized and UV-irradiated mice produced significantly larger amounts of IL-10, in an alloantigen-specific manner. Moreover, alloantigen-specific immunosuppression via CD4+ regulatory T cells was transferable to naïve B6 mice. IL-10 blocking clearly abrogated alloantigen-specific immunosuppression, indicating that UV-B irradiation evoked T regulatory type 1 cells.
Conclusions: This study demonstrates for the first time that immunization and UV irradiation induces alloantigen-specific CD4+ T regulatory type 1 cells, and that IL-10 plays an important role for this induction.

Keywords: Allografts, Liver Transplantation, T-Lymphocytes, Regulatory, Transplantation Immunology, Ultraviolet Rays

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