用于中和同种异体皮肤抗原呈递细胞的抗体功能化肽膜
Antibody-functionalized peptidic membranes for neutralization of allogeneic skin antigen-presenting cells.
作者信息
Wen Yi, Liu Wen, Bagia Christina, Zhang Shaojuan, Bai Mingfeng, Janjic Jelena M, Giannoukakis Nick, Gawalt Ellen S, Meng Wilson S
机构信息
Division of Pharmaceutical Sciences, Duquesne University, PA, USA.
Department of Radiology, University of Pittsburgh, PA, USA.
出版信息
Acta Biomater. 2014 Nov;10(11):4759-4767. doi: 10.1016/j.actbio.2014.08.003. Epub 2014 Aug 10.
We report herein application of an in situ material strategy to attenuate allograft T cell responses in a skin transplant mouse model. Functionalized peptidic membranes were used to impede trafficking of donor antigen-presenting cells (dAPCs) from skin allografts in recipient mice. Membranes formed by self-assembling peptides (SAPs) presenting antibodies were found to remain underneath grafted skins for up to 6 days. At the host-graft interface, dAPCs were targeted by using a monoclonal antibody that binds to a class II major histocompatibility complex (MHC) molecule (I-A(d)) expressed exclusively by donor cells. Using a novel cell labeling near-infrared nanoemulsion, we found more dAPCs remained in allografts treated with membranes loaded with anti-I-A(d) antibodies than without. In vitro, dAPCs released from skin explants were found adsorbed preferentially on anti-I-A(d) antibody-loaded membranes. Recipient T cells from these mice produced lower concentrations of interferon-gamma cultured ex vivo with donor cells. Taken together, the data indicate that the strategy has the potential to alter the natural course of rejection immune mechanisms in allogeneic transplant models.
我们在此报告一种原位材料策略在皮肤移植小鼠模型中减弱同种异体移植T细胞反应的应用。功能化肽膜用于阻止供体抗原呈递细胞(dAPC)从受体小鼠的皮肤同种异体移植物中迁移。发现由呈现抗体的自组装肽(SAP)形成的膜在移植皮肤下可保留长达6天。在宿主 - 移植物界面,通过使用与仅由供体细胞表达的II类主要组织相容性复合体(MHC)分子(I-A(d))结合的单克隆抗体来靶向dAPC。使用一种新型的细胞标记近红外纳米乳剂,我们发现与未负载抗I-A(d)抗体的膜处理的同种异体移植物相比,负载抗I-A(d)抗体的膜处理的同种异体移植物中保留了更多的dAPC。在体外,发现从皮肤外植体释放的dAPC优先吸附在负载抗I-A(d)抗体的膜上。来自这些小鼠的受体T细胞与供体细胞在体外培养时产生较低浓度的干扰素 - γ。综上所述,数据表明该策略有可能改变同种异体移植模型中排斥免疫机制的自然进程。