Targeting antigen-specific T cells by genetically engineered antigen presenting cells: A strategy for specific immunotherapy of autoimmune disease

  • Wu J
  • Wu B
  • Guarnieri F
 et al. 
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We describe a strategy for specific immunotherapy of autoimmune disease based on targeting the antigen-specific T cells in an experimental model of myasthenia gravis. To address the problem of heterogeneity of the T cell repertoire, we have genetically engineered antigen presenting cells (APCs) to process and present epitopes of the autoantigen, acetylcholine receptor (AChR), to the entire spectrum of AChR-specific syngeneic T cells. APCs derived from BALB/c mice were stably transfected with cDNA for the key immunogenic domain of the AChR α-subunit, flanked by sequences of the lysosome-associated membrane protein (LAMP) that direct APCs to process and present the antigen via the MHC Class II pathway. Transfected APCs strongly stimulated AChR-specific T cells from BALB/c mice. Fas ligand, or antibody to Fas, abrogated the T cell response, by inducing apoptosis of the APC- stimulated T cells. The new results of this investigation are (1) that autoreactive T cells can be effectively targeted by autologous APCs that are engineered to present the relevant autoantigen, and (2) that these specifically targeted and activated T cells can be profoundly inhibited by agents that trigger the Fas-mediated apoptosis pathway. The present findings suggest that engineering APCs for simultaneous presentation of the autoantigen and delivery of FasL will provide a powerful strategy for the elimination of autoreactive T cells. (C) 2000 Elsevier Science B.V.

Author-supplied keywords

  • Antigen-specific T cells
  • Autoimmune disease
  • Genetic engineering
  • Immunotherapy

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  • Jian Ming Wu

  • Bo Wu

  • Frank Guarnieri

  • J. Thomas August

  • Daniel B. Drachman

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