Publications [#278111] of Chi Wei C. Chan

Papers Published

1. Tan, PH; Yates, JB; Xue, S-A; Chan, C; Jordan, WJ; Harper, JE; Watson, MP; Dong, R; Ritter, MA; Lechler, RI; Lombardi, G; George, AJT, Creation of tolerogenic human dendritic cells via intracellular CTLA4: a novel strategy with potential in clinical immunosuppression., Blood, vol. 106 no. 9 (November, 2005), pp. 2936-2943, ISSN 0006-4971 [15994283], [doi]
   (last updated on 2026/01/16)

   Abstract:
   Activation of T lymphocytes requires the recognition of peptide-major histocompatibility complexes (MHCs) and costimulatory signals provided by antigen-presenting cells (APCs). It has been shown that T-cell activation without costimulation can lead to anergy. In this study, we developed a novel strategy to inhibit expression of B7 molecules (CD80/86) by transfecting APCs with a gene construct encoding a modified cytotoxic T lymphocyte antigen 4 (CTLA4) molecule (CTLA4-KDEL) that is targeted to the endoplasmic reticulum (ER). APCs expressing this construct failed to express CD80/86 on their surface, were unable to stimulate allogeneic and peptide-specific T-cell responses, and induced antigen-specific anergy of the responding T cells. Cells expressing CTLA4-KDEL do not up-regulate the indoleamine 2, 3-dioxygenase enzyme, unlike cells treated with soluble CTLA4-immunoglobin (Ig). This gene-based strategy to knock out surface receptors is an attractive alternative to using immature dendritic cells for preventing transplant rejection and treating of autoimmune diseases.

   Keywords:
   Antigens, CD • Antigens, Differentiation • B-Lymphocytes • CTLA-4 Antigen • Cell Line • Cell Proliferation • Coculture Techniques • Dendritic Cells • Humans • Immune Tolerance • Immunosuppression • T-Lymphocytes • Transfection • cytology • genetics • immunology • immunology* • metabolism • metabolism* • methods*