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Blockade of LIGHT/LTβ and CD40 signaling induces allospecific T cell anergy, preventing graft-versus-host disease

Year: 2002
Type: article
Abstract: Previous studies have shown that blockade of LIGHT, a T cell costimulatory molecule belonging to the TNF superfamily, by soluble lymphotoxin β receptor–Ig (LTβR-Ig) inhibits the cytotoxic T lymphocyte (CTL) response to host antigenic disparities and ameliorates lethal graft-versus-host disease (GVHD) in a B6 to BDF1 mouse model. Here, we demonstrate that infusion of an mAb against CD40 ligand (CD40L) further increases the efficacy of LTβR-Ig, leading to complete prevention of GVHD. We further demonstrate that alloantigen-specific CTLs become anergic upon rapid expansion, and persist in the tolerized mice as a result of costimulatory blockade. Transfer of anergic CTLs to secondary F1 mice fails to induce GVHD despite the fact that anergic CTLs can be stimulated to proliferate in vitro by antigens and cytokines. Our study provides a potential new approach for the prevention of lethal GVHD.
DOI: 10.1172/jci13604
Authors: Koji Tamada, Hideto Tamura, Dallas Flies, Yang-Xin Fu, Esteban Celis, Larry R. Pease, Bruce R. Blazar, Lieping Chen
Language: English
Subfield: Immunology
Open Access status: green
Funders: American Cancer Society, Mayo Foundation for Medical Education and Research, National Natural Science Foundation of China, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases
Awards: G1131893199, G1132825990, T-Cell Targeting for GVHD, In vivo Prevention of Murine GVHD, G3153773428, G546021563, G666159279, T CELL TARGETING FOR GVHD, Experimental Therapy of Cancer by Costimulated Immunity
OpenAlex ID: W4243951751
FWCI: 0.329
Cites: 47
Cited by: 20
Related to: 10