期刊
ONCOTARGET
卷 7, 期 11, 页码 12176-12190出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.7519
关键词
autoimmune disease; allograft rejection; PLGA; p/MHC; alloreactive T cells; Immunology and Microbiology Section; Immune response; Immunity
资金
- National Natural Science Foundation of China [81172823, 81372448]
- Science and Technology Support Program of Jiangsu Province [BE2012739]
- Fundamental Research Funds for the Central Universities of China
- Post-graduate Research & Innovation Program of Jiangsu province [KYLX-0194]
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) antigentargeted killer MPs significantly depleted OVA-specific CD8(+) T cells in an antigenspecific 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-2K(b) 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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