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Blockade of costimulatory CD27/CD70 pathway promotes corneal allograft survival.
Experimental Eye Research ( IF 3.4 ) Pub Date : 2020-08-14 , DOI: 10.1016/j.exer.2020.108190
Akitomo Narimatsu 1 , Takaaki Hattori 1 , Yoshihiko Usui 1 , Hiroki Ueno 2 , Toshinari Funaki 3 , Hiroyuki Komatsu 1 , Hayate Nakagawa 1 , Hisaya Akiba 4 , Hiroshi Goto 1
Affiliation  

Purpose

To determine whether the CD27/CD70 pathway plays a significant role in corneal allograft rejection by investigating the effect of blocking the CD27/CD70 pathway by anti-CD70 antibody on corneal allograft survival.

Methods

Orthotopic penetrating keratoplasty was performed using C57BL/6 donor grafts and BALB/c recipients. Expression of CD27 and CD70 on rejected cornea was examined by immunohistochemistry. Corneal transplant recipients received intraperitoneal injection of anti-CD70 antibody (FR70) or control rat IgG. Alloreactivity was measured by mixed lymphoid reaction (MLR) in recipients administered control rat IgG and those administered anti-CD70 antibody. Corneal expression of IFN-γ and IL-12 was also examined in both groups. Graft opacity was assessed over an 8-week period and graft survival was evaluated using Kaplan-Meier survival curves. Proportion of CD4+CD44+ memory T cells in lymph nodes was measured by flow cytometry.

Results

CD4+CD27+ cells and CD11c+CD70+ cells were present in rejected cornea. Anti-CD70 antibody administration suppressed alloreactivity in corneal allograft recipients, and inhibited IFN-γ expression in recipient cornea (p < 0.05). Anti-CD70 antibody suppressed opacity score of recipient cornea and prolonged corneal allograft survival (p < 0.05). Proportion of CD4+CD44+ memory T cells in recipient lymph nodes was reduced by anti-CD70 antibody treatment.

Conclusion

The CD27/CD70 pathway plays a significant role in corneal allograft rejection by initiating alloreactive Th1 cells and preserving memory T cells. Anti-CD70 antibody administration prolongs corneal allograft survival indicating the potential therapeutic effect of CD27/CD70 pathway blockade on corneal allograft rejection.



中文翻译:

共刺激CD27 / CD70途径的阻断促进了角膜同种异体移植物的存活。

目的

通过研究抗CD70抗体阻断CD27 / CD70途径对角膜同种异体移植存活的影响,确定CD27 / CD70途径在角膜同种异体移植排斥中是否起重要作用。

方法

使用C57BL / 6供体移植物和BALB / c受者进行原位穿透性角膜移植手术。通过免疫组织化学检查在排斥的角膜上CD27和CD70的表达。角膜移植受者接受腹膜内注射抗CD70抗体(FR70)或对照大鼠IgG。通过混合淋巴样反应(MLR)在接受对照大鼠IgG和接受抗CD70抗体的接受者中测量同种异体反应性。两组均检查了角膜IFN-γ和IL-12的表达。在8周的时间内评估了移植物的不透明度,并使用Kaplan-Meier存活曲线评估了移植物的存活率。通过流式细胞术测量CD4 + CD44 +记忆T细胞在淋巴结中的比例。

结果

在排斥的角膜中存在CD4 + CD27 +细胞和CD11c + CD70 +细胞。抗CD70抗体的给药抑制了同种异体角膜移植受者的同种异体反应,并抑制了受体角膜中的IFN-γ表达(p  <0.05)。抗CD70抗体抑制了受体角膜的不透明度评分并延长了同种异体角膜的存活率(p  <0.05)。抗CD70抗体治疗降低了受体淋巴结中CD4 + CD44 +记忆T细胞的比例。

结论

CD27 / CD70途径通过启动同种反应性Th1细胞并保存记忆T细胞,在异体角膜移植排斥中起重要作用。抗CD70抗体的给药延长了角膜同种异体移植物的存活,表明CD27 / CD70途径阻断对角膜同种异体移植物排斥的潜在治疗作用。

更新日期:2020-08-24
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