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17 October 2014 : Original article  

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 HoriBCD, Kagemasa KuribayashiA, Kanako SaitoB, Linan WangB, Mie ToriiB, Shinji UemotoA, Takuma KatoA

DOI: 10.12659/AOT.890890

Ann Transplant 2014; 19:519-536


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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Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358