Killer artificial antigen-presenting cells: a novel strategy to delete specific T cells.
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.
Schütz
Christian
C
Department of Internal Medicine I, University of Regensburg, Germany. christian.schuetz@klinik.uni-r.de
Fleck
Martin
M
Mackensen
Andreas
A
Zoso
Alessia
A
Halbritter
Dagmar
D
Schneck
Jonathan P
JP
Oelke
Mathias
M
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000737:chemistry / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000737:chemistry / Q000276:immunology*; D008212:Lymphocyte Depletion / Q000379:methods*; D008863:Microspheres; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D014184:Transplantation, Homologous; D019014:fas Receptor / Q000737:chemistry / Q000276:immunology*
D000911:Antibodies, Monoclonal; D053222:Fas Ligand Protein; D007075:Immunoglobulin M; D019014:fas Receptor