TY - JOUR
T1 - Killer artificial antigen-presenting cells
T2 - A novel strategy to delete specific T cells
AU - Schütz, Christian
AU - Fleck, Martin
AU - Mackensen, Andreas
AU - Zoso, Alessia
AU - Halbritter, Dagmar
AU - Schneck, Jonathan P.
AU - Oelke, Mathias
PY - 2008/4/1
Y1 - 2008/4/1
N2 - 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 (κaAPCs) by coupling an apoptosis-inducing α-Fas (CD95) IgM mAb together with HLA-A2 Ig molecules onto beads. These κaAPCs 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 κaAPCs and independent of activation-induced cell death (AICD). κaAPCs 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.
AB - 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 (κaAPCs) by coupling an apoptosis-inducing α-Fas (CD95) IgM mAb together with HLA-A2 Ig molecules onto beads. These κaAPCs 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 κaAPCs and independent of activation-induced cell death (AICD). κaAPCs 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.
UR - http://www.scopus.com/inward/record.url?scp=43549095277&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=43549095277&partnerID=8YFLogxK
U2 - 10.1182/blood-2007-09-113522
DO - 10.1182/blood-2007-09-113522
M3 - Article
C2 - 18096763
AN - SCOPUS:43549095277
SN - 0006-4971
VL - 111
SP - 3546
EP - 3552
JO - Blood
JF - Blood
IS - 7
ER -