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.
Department of Pathology, College of Medicine, Seoul National University, Seoul 151-742, South Korea.
Kyeong Cheon
KC
Jung
Chung-Gyu
CG
Park
Yoon Kyung
YK
Jeon
Hyo Jin
HJ
Park
Young Larn
YL
Ban
Hye Sook
HS
Min
Eun Ji
EJ
Kim
Ju Hyun
JH
Kim
Byung Hyun
BH
Kang
Seung Pyo
SP
Park
Youngmee
Y
Bae
Il-Hee
IH
Yoon
Yong-Hee
YH
Kim
Jae-Il
JI
Lee
Jung-Sik
JS
Kim
Jun-Seop
JS
Shin
Jaeseok
J
Yang
Sung Joo
SJ
Kim
Emily
E
Rostlund
William A
WA
Muller
Seong Hoe
SH
Park
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018952:Antigens, CD34 / Q000008:administration & dosage; D003713:Dendritic Cells / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000008:administration & dosage; D016381:Islets of Langerhans Transplantation; D008253:Macaca mulatta; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D018799:Intercellular Adhesion Molecule-1