A biodegradable killer microparticle to selectively deplete antigen-specific T cells in vitro and in vivo.
A biodegradable killer microparticle to selectively deplete antigen-specific T cells in vitro and in vivo.
复制标题
一种可生物降解的杀伤微粒，可在体外和体内选择性地消耗抗原特异性 T 细胞
DOI：
10.18632/oncotarget.7519
复制
发表时间：
2016-03-15
期刊：
影响因子：
--
通讯作者：
Shen CL
中科院分区：
文献类型：
--
作者：
Wang W;Fang K;Li MC;Chang D;Shahzad KA;Xu T;Zhang L;Gu N;Shen CL
在不损害整体免疫功能的情况下，特异性根除致病T细胞是治疗同种异体移植排斥反应和自身免疫性疾病的根本目标。本文制备了细胞大小的聚乳酸-乙醇酸共聚微球(PLGA MPS)作为支架，共展示多肽/主要组织相容性复合体(pMHC，靶抗原)和抗Fas单抗(凋亡诱导分子)，以生成可生物降解的杀伤MPS。在体外和OT-1小鼠中，卵蛋白(OVA)抗原靶向的杀伤MPS以抗原特异性的方式显著耗尽OVA特异的CD8+T细胞。静脉给药后，杀伤性MPS主要聚集在OT-1小鼠的肝、肺和肠道中，保留时间长达48小时。MPS的杀灭作用在两次注射后持续4天。此外，H-2kb靶向同种异体抗原的杀伤MPS能够消除低频同种异体反应性T细胞，并将bm1小鼠的同种异体皮肤移植物存活时间延长41.5天。我们的数据表明，基于PLGA的杀伤MPS能够特异性地消耗致病T细胞，这突显了它们在治疗同种异体移植排斥反应和自身免疫性疾病方面的治疗潜力。
The specific eradication of pathogenic T cells for the treatment of allograft rejections and autoimmune disorders without impairment of overall immune function is a fundamental goal. Here, cell-sized poly(lactic-co-glycolic acid) microparticles (PLGA MPs) were prepared as a scaffold to co-display the peptide/major histocompatibility complex (pMHC, target antigen) and anti-Fas monoclonal antibody (apoptosis-inducing molecule) for the generation of biodegradable killer MPs. Ovalbumin (OVA) antigen-targeted killer MPs significantly depleted OVA-specific CD8+ T cells in an antigen-specific manner, both in vitro and in OT-1 mice. After intravenous administration, the killer MPs predominantly accumulated in the liver, lungs, and gut of OT-1 mice with a retention time of up to 48 hours. The killing effects exerted by killer MPs persisted for 4 days after two injections. Moreover, the H-2Kb alloantigen-targeted killer MPs were able to eliminate low-frequency alloreactive T cells and prolong alloskin graft survival for 41.5 days in bm1 mice. Our data indicate that PLGA-based killer MPs are capable of specifically depleting pathogenic T cells, which highlights their therapeutic potential for treating allograft rejection and autoimmune disorders.