Fukushima A, Yamaguchi T, Azuma M, Yagita H, Ueno H
Department of Ophthalmology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku-city 783-8505, Japan.
Br J Ophthalmol. 2006 Aug;90(8):1040-5. doi: 10.1136/bjo.2006.091314. Epub 2006 Apr 13.
BACKGROUND/AIM: Involvement of programmed death-1 (PD-1) and its ligands has been demonstrated in experimental allergic airway disease. Here, the authors aimed to examine whether PD-1 and its ligands are involved in the development of experimental allergic conjunctivitis (EC) in mice.
EC was induced in Balb/c mice by active immunisation with short ragweed pollen (RW) in alum. 10 days later (day 10), the mice were challenged with eye drops containing RW. 24 hours after the challenge, conjunctivas, spleens, and sera were harvested for histological analysis, cytokine assays, and measurement of RW specific Ig levels. The actively immunised mice were treated with anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies (Abs), or normal rat immunoglobulin G (nrIgG) during either the induction (day 0, 2, 4, 6, and 8) or the effector (2 hours before RW challenge on day 10) phase.
Ab treatment during the induction phase did not affect eosinophil infiltration although immune responses were modulated. In contrast, treatment with anti-PD-L2 Ab, but not anti-PD-1 or anti-PD-L1 Ab, during the effector phase significantly increased eosinophil infiltration into the conjunctiva without affecting systemic immune responses.
Similar to allergic airway inflammation, PD-L2 is involved in the development of EC during the effector phase but not the induction phase.
背景/目的:程序性死亡-1(PD-1)及其配体在实验性变应性气道疾病中的作用已得到证实。在此,作者旨在研究PD-1及其配体是否参与小鼠实验性变应性结膜炎(EC)的发生发展。
通过在明矾中用短豚草花粉(RW)主动免疫Balb/c小鼠诱导EC。10天后(第10天),用含RW的滴眼液对小鼠进行激发。激发后24小时,采集结膜、脾脏和血清进行组织学分析、细胞因子检测以及RW特异性Ig水平测定。在诱导期(第0、2、4、6和8天)或效应期(第10天RW激发前2小时),对主动免疫的小鼠用抗PD-1、抗PD-L1、抗PD-L2抗体(Abs)或正常大鼠免疫球蛋白G(nrIgG)进行治疗。
诱导期抗体治疗虽可调节免疫反应,但不影响嗜酸性粒细胞浸润。相反,效应期用抗PD-L2抗体而非抗PD-1或抗PD-L1抗体治疗可显著增加结膜中嗜酸性粒细胞浸润,且不影响全身免疫反应。
与变应性气道炎症相似,PD-L2在效应期而非诱导期参与EC的发生发展。