title: Killer artificial antigen-presenting cells deplete alloantigen-specific T cells in a murine model of alloskin transplantation.
abstract: FasL-expressing killer antigen-presenting cells (KAPCs) have the ability to delete antigen-specific T cells and, therefore, could potentially be used for the treatment of allograft rejection and autoimmunity; however, their cellular nature markedly limits their clinical use. Novel bead-based killer artificial antigen-presenting cells (KaAPCs), which are generated by coupling major histocompatibility complex (MHC) class I antigens together with the apoptosis-inducing anti-Fas monoclonal antibody (mAb) onto magnetic beads, have recently attracted more attention. KaAPCs have a number of advantages over KAPCs and are able to deplete specific T cells in cocultures. However, it remains unknown whether bead-based KaAPCs can also induce apoptosis of alloreactive or autoreactive T cells and, consequently, generate hyporesponsiveness in vivo. In this study, H-2K(b)/peptide monomers and anti-Fas mAb have been covalently coupled to latex beads and administered intravenously into BALB/c mice (H-2K(d)) that had previously been grafted with skin squares from C57BL/6 mice (H-2K(b)). Alloskin graft survival was prolonged for 6 days. A 60% decrease of H-2K(b) antigen-alloreactive T cells was demonstrated by several measures 2 days after each injection of KaAPCs, but intact immune function, including antitumor activity, was maintained. These data provide the first in vivo evidence that bead-based KaAPCs can selectively deplete antigen-specific T cells without the loss of overall immune responsiveness and, therefore, highlight the therapeutic potential of this novel strategy for the treatment of allograft rejection and autoimmune disorders.
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Southeast University School of Medicine, Nanjing, Jiangsu, China.
authors.forename: Chuanlai
authors.initials: C
authors.lastname: Shen
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Kai
authors.initials: K
authors.lastname: Cheng
authors.forename: Daoping
authors.initials: D
authors.lastname: Zhang
authors.forename: Shenwei
authors.initials: S
authors.lastname: Miao
authors.forename: Aifeng
authors.initials: A
authors.lastname: Zhang
authors.forename: Fanyan
authors.initials: F
authors.lastname: Meng
authors.forename: Fengqin
authors.initials: F
authors.lastname: Miao
authors.forename: Jianqiong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D000938:Antigen-Presenting Cells / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D058045:Artificial Cells / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D053222:Fas Ligand Protein / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007108:Immune Tolerance; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D007275:Injections, Intravenous; D008212:Lymphocyte Depletion; D008280:Magnetics / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008863:Microspheres; D023421:Models, Animal; D016038:Skin Transplantation / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D053222:Fas Ligand Protein; D015395:Histocompatibility Antigens Class I; D018796:Immunoconjugates; C411023:anti-Fas monoclonal antibody