演題詳細

一般口演 / Oral Session

一般口演 22 (Oral Session 22) :造血幹細胞移植:基礎

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日程
2013年10月11日(金)
時間
15:25 - 16:25
会場
第5会場 / Room No.5 (さっぽろ芸文館 3F 清流)
座長・司会
村田 誠 (Makoto Murata):1
1:名古屋大学医学部附属病院 血液内科
 
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PD-1 pathway of donors and recipients modulate chronic graft-versus-host disease in mouse model

演題番号 : OS-1-114

藤原 英晃 (Hideaki Fujiwara):1、前田 嘉信 (Yoshinobu Maeda):1、小林 孝一郎 (Koichiro Kobayashi):1、西森 久和 (Hisakazu Nishimori):1、西之原 正昭 (Masaaki Nishinohara):1、岡本 幸代 (Sachiyo Okamoto):1、松岡 賢市 (Ken-Ichi Matsuoka):1、近藤 英生 (Eisei Kondo):1、藤井 伸治 (Nobuharu Fujii):1、品川 克至 (Katsuji Shinagawa):1、谷本 光音 (Mitsune Tanimoto):1

1:Dept. of Hematology and Oncology Okayama University Hospital

 

Background:Relationship between chronic graft-versus-host disease (cGVHD) and inhibitory signals remains unclear. Here, we report on contribution of PD-1 pathway to cGVHD. Method:We investigated the roles of the PD-1 pathway in cGVHD using B10.D2 into BALB/c model. Expression levels of PD-1 and B7H1 on donor cells were analyzed by flow cytometry. Expressions of B7H1 on tissue of the recipients were analyzed by immunohistochemistry and real-time PCR. To examine the roles of the PD-1 axis, we used PD-1 KO and B7H1 KO mice. Result:CD4 and CD8 cells from the spleen and peripheral lymph nodes (LNs) of allogeneic recipients expressed significantly more PD-1 compared to syngeneic recipients (p<0.05). mRNA levels of B7H1 from the LNs and skin of the allogeneic recipients were also elevated from day14 to day28 (p<0.05), while, from day 28 onward, expressions of B7H1 from the allogeneic recipients decreased. Administration of anti-B7H1 Ab significantly exacerbated cGVHD in allogeneic recipients and allogeneic B7H1 KO recipients showed significantly more severe skin cGVHD than controls (p<0.05). Histopathological examination of the skin showed significantly increased cGVHD damage in recipients of B7H1 KO donors (p<0.05). IL-17+ IFNg+ T cells were detected significantly more frequently in recipients of B7H1 KO donors than those of WT recipients (day 28, p<0.05), meanwhile regulatory T cells were similar. Conclusion:Taken together, the PD-1 axis, especially B7H1 expression on recipients, regulates the frequency of IL-17+ IFNg+ T cells and contributes to the pathogenesis of cGVHD.

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