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  • Killer artificial antigen-presenting cells: a novel strategy to delete specific T cells.

Killer artificial antigen-presenting cells: a novel strategy to delete specific T cells.

Blood (2007-12-22)
Christian Schütz, Martin Fleck, Andreas Mackensen, Alessia Zoso, Dagmar Halbritter, Jonathan P Schneck, Mathias Oelke
ABSTRACT

Several cell-based immunotherapy strategies have been developed to specifically modulate T cell-mediated immune responses. These methods frequently rely on the utilization of tolerogenic cell-based antigen-presenting cells (APCs). However, APCs are highly sensitive to cytotoxic T-cell responses, thus limiting their therapeutic capacity. Here, we describe a novel bead-based approach to modulate T-cell responses in an antigen-specific fashion. We have generated killer artificial APCs (kappaaAPCs) by coupling an apoptosis-inducing alpha-Fas (CD95) IgM mAb together with HLA-A2 Ig molecules onto beads. These kappaaAPCs deplete targeted antigen-specific T cells in a Fas/Fas ligand (FasL)-dependent fashion. T-cell depletion in cocultures is rapidly initiated (30 minutes), dependent on the amount of kappaaAPCs and independent of activation-induced cell death (AICD). kappaaAPCs represent a novel technology that can control T cell-mediated immune responses, and therefore has potential for use in treatment of autoimmune diseases and allograft rejection.

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Sigma-Aldrich
Monoclonal Anti-CD8−FITC antibody produced in mouse, clone UCHT-4, purified immunoglobulin, buffered aqueous solution