Kyeong Cheon Jung1,2, Chung-Gyu Park3,4,8, Yoon Kyung Jeon1, Hyo Jin Park1, Young Larn Ban2, Hye Sook Min1, Eun Ji Kim2, Ju Hyun Kim1, Byung Hyun Kang2, Seung Pyo Park7, Youngmee Bae5, Il-Hee Yoon3,4,8, Yong-Hee Kim3,4,8, Jae-Il Lee8, Jung-Sik Kim3,4,8, Jun-Seop Shin3,4,8, Jaeseok Yang6,9, Sung Joo Kim10,11, Emily Rostlund12, William A. Muller12, and Seong Hoe Park1,2
1Department of Pathology, 2Graduate School of Immunology, 3Department of Microbiology and Immunology, 4Cancer Research Institute, 5Department of Parasitology and Tropical Medicine, and 6Transplantation Research Institute, College of Medicine; and 7National Creative Research Initiative Center for Oxide Nanocrystalline Materials, School of Chemical and Biological Engineering, College of Engineering; Seoul National University, Seoul 151-742, South Korea 8Xenotransplantation Research Center and Transplantation Center, Seoul National University Hospital, Seoul 110-744, South Korea 10Department of Surgery and 11Department of Molecular Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, South Korea 12Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611
K.C. Jung and C.-G. Park contributed equally to this paper.
CORRESPONDENCE Seong Hoe Park
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.