Hori Tomohide, Kuribayashi Kagemasa, Saito Kanako, Wang Linan, Torii Mie, Uemoto Shinji, Kato Takuma
Department of Transplant Surgery, Kyoto University Hospital, Kyoto, Japan.
Department of Cellular and Molecular Immunology, Mie University Graduate School of Medicine, Tsu, Japan.
Ann Transplant. 2014 Oct 17;19:519-36. doi: 10.12659/AOT.890890.
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.
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.
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.
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.
紫外线（UV）-B照射在同种抗原免疫后使用的情况尚不清楚，因为先前的研究集中在免疫前的UV-B照射。在此，我们研究了免疫后UV-B照射诱导的免疫抑制作用，并检测了诱导调节性T细胞的表型及诱导的可能机制。
用CBF1小鼠（H-2(b/d)）的脾细胞对B6小鼠（H-2(b)）进行静脉免疫。同种抗原免疫一周后，B6小鼠接受高剂量UV-B照射（40 kJ/m(2)）。UV-B照射四周后，进行增殖试验（每组n = 4）、皮肤或心脏同种异体移植（每组n = 5）、混合淋巴细胞培养中的细胞因子检测（每组n = 6）以及将CD4(+) T细胞过继转移至未致敏的B6小鼠（每组n = 5）。小鼠分为4组：未处理对照、免疫对照、UV照射对照以及免疫加UV照射组。用B6C3F1小鼠（H-2(b/k)）作为免疫对照的无关同种抗原。在UV-B照射前后使用抗IL-10单克隆抗体阻断IL-10。
免疫加UV照射的小鼠对免疫抗原的免疫反应以同种抗原特异性方式受到显著抑制。令人惊讶的是，免疫加UV照射小鼠的CD4(+) T细胞以同种抗原特异性方式产生显著更多的IL-10。此外，通过CD4(+)调节性T细胞的同种抗原特异性免疫抑制可转移至未致敏的B6小鼠。IL-10阻断明显消除了同种抗原特异性免疫抑制，表明UV-B照射诱导了1型调节性T细胞。
本研究首次证明免疫和UV照射诱导了同种抗原特异性CD4(+) 1型调节性T细胞，且IL-10在该诱导过程中起重要作用。
