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Specific deletion of autoreactive T cells by adenovirus-transfected, fas ligand-producing antigen-presenting cells

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Abstract

Immune privilege is a unique strategy developed in several internal organs that can prevent the development of immune attack against these vital organs. One critical mechanism of immune privilege is utilizati of Fas/FasL-mediated apoptosis to delete the invading T cells at the immune privilege sites. In this article, we describe the development and application of a unique cell-gene therapy to correct defective FasL-mediated apoptosis and autoimmune disease in autoimmune mice. This cell-gene therapy strategy using antigen-presenting cells (APCs) to express FasL is not only a therapeutic tool, but also has allowed us to understand the complexity of T cell regulation and the concept of eliminating T cells in the spleen, lymph node, orelse where in vivo to regulate the homeostasis of the peripheral T cell response. In this regard, the FasL-expressing APCs can be considered as circulating and regulatable immune privilege sites. Our studies provide substantial evidence that FasL-expressing APCs can be introduced exogenously without liver toxicity to eliminate infiltrating T cells and prevent the development of immune attack in lung, liver, kidney, joint, and salivary gland. Therefore, given the hazardous potential of persistent T cell invasion at the local inflammatory site, it is tempting to speculate that such an endogenous control mechanism occurs normally in vivo to limit a chronic T cell inflammatory response.

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Authors and Affiliations

  1. Department of Medicine, University of Alabama at Birmingham, 35294, Birmingham, AL

    Huang-Ge Zhang, John D. Mountz MD, PhD, Tong Zhou & Hui-Chen Hsu

  2. Veterans Administration Medical Center, Birmingham, AL

    Huang-Ge Zhang & John D. Mountz MD, PhD

  3. Department of Medicine, University of Regensburg, Regensburg, Germany

    Martin Fleck

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  1. Huang-Ge Zhang
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  2. John D. Mountz MD, PhD
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  3. Martin Fleck
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  4. Tong Zhou
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  5. Hui-Chen Hsu
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Correspondence to John D. Mountz MD, PhD.

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Zhang, HG., Mountz, J.D., Fleck, M. et al. Specific deletion of autoreactive T cells by adenovirus-transfected, fas ligand-producing antigen-presenting cells. Immunol Res 26, 235–246 (2002). https://doi.org/10.1385/IR:26:1-3:235

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