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

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.This study was supported by a grant from the Korea Biotech R&D Group of Next-Generation Growth Engine Project of the Ministry of Education, Science and Technology, Republic of Korea (Project no. 2010K001294; to K.C. Jung), a grant from Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (Project No.A040004; to C.-G. Park), and grants from the United States National Institutes of Health (R01 HL046849 and R37 HL06774; to W.A. Muller)