title: A biodegradable killer microparticle to selectively deplete antigen-specific T cells in vitro and in vivo.
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.
authors.affiliation: Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Fang
authors.affiliation: Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, PR China.
authors.forename: Miao-Chen
authors.initials: MC
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Chang
authors.affiliation: Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, PR China.
authors.forename: Khawar Ali
authors.initials: KA
authors.lastname: Shahzad
authors.affiliation: Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
authors.affiliation: Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, PR China.
authors.forename: Chuan-Lai
authors.initials: CL
authors.lastname: Shen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D008212:Lymphocyte Depletion / Q000379:methods*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018984:Epitopes, T-Lymphocyte; C411023:anti-Fas monoclonal antibody; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin
keywords: Immune response; Immunity; Immunology and Microbiology Section; PLGA; allograft rejection; alloreactive T cells; autoimmune disease; p/MHC