Journal
BLOOD
Volume 111, Issue 7, Pages 3546-3552Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-09-113522
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Funding
- NCI NIH HHS [R01 CA108835] Funding Source: Medline
- NIAID NIH HHS [R01 AI44129] Funding Source: Medline
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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 (kappa aAPCs) by coupling an apoptosis-inducing alpha-Fas (CD95) IgM mAb together with HLA-A(2) 19 molecules onto beads. These kappa aAPCs 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 kappa aAPCs and independent of activation-induced cell death (AICD). kappa aAPCs 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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