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  • Title: Killer artificial antigen-presenting cells deplete alloantigen-specific T cells in a murine model of alloskin transplantation.
    Author: Shen C, He Y, Cheng K, Zhang D, Miao S, Zhang A, Meng F, Miao F, Zhang J.
    Journal: Immunol Lett; 2011 Aug 30; 138(2):144-55. PubMed ID: 21513739.
    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.
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