Research Papers: Immunology:
A biodegradable killer microparticle to selectively deplete antigen-specific T cells in vitro and in vivo
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Abstract
Wei Wang1, Kun Fang2, Miao-Chen Li1, Di Chang3, Khawar Ali Shahzad1, Tao Xu1, Lei Zhang1, Ning Gu2 and Chuan-Lai Shen1
1 Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, PR China
2 School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, PR China
3 Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, PR China
Correspondence to:
Ning Gu, email:
Chuan-Lai Shen, email:
Keywords: autoimmune disease, allograft rejection, PLGA, p/MHC, alloreactive T cells, Immunology and Microbiology Section, Immune response, Immunity
Received: October 01, 2015 Accepted: February 05, 2016 Published: February 17, 2016
Abstract
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.
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PII: 7519