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In situ induction of dendritic cell–based T cell tolerance in humanized mice and nonhuman primates
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- Authors
- Issue Date
- 2011-10
- Publisher
- Rockefeller University Press
- Citation
- J Exp Med. 2011 Oct 24. http://www.jem.org/cgi/doi/10.1084/jem.20111242
- Abstract
- Induction of antigen-specific T cell tolerance would aid treatment of diverse immunological disorders and help prevent allograft rejection and graft versus host disease. In this study, we establish a method of inducing antigen-specific T cell tolerance in situ in diabetic humanized
mice and Rhesus monkeys receiving porcine islet xenografts. Antigen-specific T cell tolerance is induced by administration of an antibody ligating a particular epitope on ICAM-1 (intercellular adhesion molecule 1). Antibody-mediated ligation of ICAM-1 on dendritic cells (DCs) led to the arrest of DCs in a semimature stage in vitro and in vivo. Ablation of DCs from mice completely abrogated anti–ICAM-1–induced antigen-specific T cell tolerance. T cell responses
to unrelated antigens remained unaffected. In situ induction of DC-mediated T cell tolerance using this method may represent a potent therapeutic tool for preventing graft rejection.
- ISSN
- 0022-1007
- Language
- English
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