Genetic engineering of dendritic cells to express immunosuppressive molecules (viral IL-10, TGF-beta, and CTLA4Ig).
There is growing evidence that, in addition to their role as initiators of immune responses, dendritic cells (DC) can exhibit tolerogenic properties. Immature DC deficient in cell surface costimulatory/accessory molecules can prolong organ and pancreatic islet allograft survival, whereas in vitro manipulation of DC by exposure to a variety of factors (e.g., viral interleukin-10; CTLA4Ig) can confer tolerogenic properties on these cells. Genetic engineering of DC to express immunosuppressive molecules is, in theory, an attractive approach to the therapy of allograft rejection and possibly, autoimmune disorders.
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Thomas E. Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh, Pennsylvania, USA. linalu+@med.pitt.edu
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Takayama
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Qian
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Gambotto
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Robbins
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Thomson
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D000069594:Abatacept; D000256:Adenoviridae; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D003713:Dendritic Cells / Q000378:metabolism*; D015870:Gene Expression; D005818:Genetic Engineering; D005822:Genetic Vectors; D006801:Humans; D007108:Immune Tolerance; D018796:Immunoconjugates; D016753:Interleukin-10 / Q000235:genetics*; D012190:Retroviridae; D016212:Transforming Growth Factor beta / Q000235:genetics*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D000069594:Abatacept