In situ induction of dendritic cell-based T cell tolerance in humanized mice and nonhuman primates

Kyeong Cheon Jung, Chung Gyu Park, Yoon Kyung Jeon, Hyo Jin Park, Young Larn Ban, Hye Sook Min, Eun Ji Kim, Ju Hyun Kim, Byung Hyun Kang, Seung Pyo Park, Youngmee Bae, Il Hee Yoon, Yong Hee Kim, Jae Il Lee, Jung Sik Kim, Jun Seop Shin, Jaeseok Yang, Sung Joo Kim, Emily Rostlund, William A. MullerSeong Hoe Park*

*Corresponding author for this work

Research output: Contribution to journalArticle

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2477-2488
Number of pages12
JournalJournal of Experimental Medicine
Volume208
Issue number12
DOIs
StatePublished - Nov 21 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Jung, K. C., Park, C. G., Jeon, Y. K., Park, H. J., Ban, Y. L., Min, H. S., Kim, E. J., Kim, J. H., Kang, B. H., Park, S. P., Bae, Y., Yoon, I. H., Kim, Y. H., Lee, J. I., Kim, J. S., Shin, J. S., Yang, J., Kim, S. J., Rostlund, E., ... Park, S. H. (2011). In situ induction of dendritic cell-based T cell tolerance in humanized mice and nonhuman primates. Journal of Experimental Medicine, 208(12), 2477-2488. https://doi.org/10.1084/jem.20111242