Antigen-Specific Killer Polylactic-Co-Glycolic Acid (PLGA) Microspheres Can Prolong Alloskin Graft Survival in a Murine Model
Antigen-Specific Killer Polylactic-Co-Glycolic Acid (PLGA) Microspheres Can Prolong Alloskin Graft Survival in a Murine Model
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抗原特异性杀伤聚乳酸-乙醇酸 (PLGA) 微球可以延长小鼠模型中同种异体皮移植物的存活时间
DOI：
10.3109/08820139.2015.1014098
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发表时间：
2015-05
影响因子：
2.8
通讯作者：
Shen Chuanlai
中科院分区：
文献类型：
--
作者：
Wang Wei;Fang Kun;Wang Xiaobing;Li Miaochen;Wu You;Chen Feng;Shahzad Khawar Ali;Gu Ning;Shen Chuanlai
背景：特异性去除抗原特异性T细胞的策略可能用于同种异体移植排斥反应和自身免疫的治疗，因为它不会抑制整个免疫系统。方法：在本研究中，我们将主要组织相容性复合体(MHC)I类抗原和诱导凋亡的抗Fas单抗(MAb)共价偶联到PLGA微球上，制备了杀伤性聚乳酸-羟基乙酸(PLGA)微球。采用改进的复乳法制备了细胞尺寸的PLGA微球。自产H-2kb/肽单体，用流式细胞仪进行分析。将杀伤性PLGA微球静脉注射到BALB/c小鼠(H-2Kd)中，将其移植到C57BL/6小鼠的皮肤方块(H-2kb)中。采用肿瘤细胞激发法和第三方混合淋巴细胞培养法检测宿主的一般免疫功能。结果：移植皮片存活时间延长4 d。杀伤PLGA微球可以特异性地耗尽渗入同种异体皮肤移植物的H-2kb同种异体抗原反应性CD8+T细胞，而不是CD4+T细胞，而不会损害宿主的整体免疫功能。结论：在此，我们初步报道了广泛用作药物载体的PLGA微球被用于制备抗原特异性杀伤复合体和治疗同种异体移植排斥反应。我们的数据突出了这种生物相容和可生物降解的抗原特异性杀伤效应器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。
Background: The strategy of specifically depleting antigen-specific T cells can potentially be used for the treatment of allograft rejection and autoimmunity because it does not suppress the overall immune systems. Methods: In this study, we generated killer polylactic-co-glycolic acid (PLGA) microspheres by covalently coupling major histocompatibility complex (MHC) class I antigens and apoptosis-inducing anti-Fas monoclonal antibody (mAb) onto PLGA microspheres. A modified double-emulsion method was used for the preparation of cell-sized PLGA microspheres. H-2Kb/peptide monomers were generated in-house and analyzed through flow cytometry. The killer PLGA microspheres were administered intravenously into BALB/c mice (H-2Kd) that had previously been grafted with skin squares from C57BL/6 mice (H-2Kb). Tumor cell challenge and third-party mixed lymphocyte culture were used to assess the general immune functions of host. Results: The alloskin graft survival was prolonged by 4 days. The killer PLGA microspheres could specifically deplete the H-2Kb alloantigen-reactive CD8+ T cells that infiltrated into the alloskin graft but not CD4+ T cells, without impairment of host overall immune function. Conclusions: Here, we initially report that PLGA microspheres, which have been widely used as medicine-delivering carriers, were used to prepare antigen-specific killer complexes and treat allograft rejection. Our data highlight the therapeutic potential of this biocompatible and biodegradable antigen-specific killer effector for the treatment of allograft rejection and autoimmune disease.
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影响因子：
5
作者：
Makadia HK;Siegel SJ
通讯作者：
Siegel SJ
影响因子：
2.5
作者：
Constantin, Carolyn M;Bonney, Elizabeth E;Strickland, Ora L
通讯作者：
Strickland, Ora L
影响因子：
20.3
作者：
K. Whartenby;E. Straley;Heeje Kim;F. Racke;V. Tanavde;K. Gorski;Linzhao Cheng;D. Pardoll;C. Ci
通讯作者：
K. Whartenby;E. Straley;Heeje Kim;F. Racke;V. Tanavde;K. Gorski;Linzhao Cheng;D. Pardoll;C. Ci
影响因子：
3.1
作者：
Chuanlai Shen;Chien-Chung Chang;Jianqiong Zhang;W. Guo;Lingzhi Xia;F. Meng;W. Xie
通讯作者：
Chuanlai Shen;Chien-Chung Chang;Jianqiong Zhang;W. Guo;Lingzhi Xia;F. Meng;W. Xie
DOI：
10.4049/jimmunol.169.9.4867
发表时间：
2002-11
期刊：
The Journal of Immunology
影响因子：
--
作者：
T. Wolfe;C. Asseman;A. Hughes;H. Matsue;A. Takashima;M. V. von Herrath
通讯作者：
T. Wolfe;C. Asseman;A. Hughes;H. Matsue;A. Takashima;M. V. von Herrath