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Lookup NU author(s): Dr Shoba Amarnath
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Immunotherapy using regulatory T cells (Treg) has been proposed, yet cellular and molecular mechanisms of human Tregs remain incompletely characterized. Here, we demonstrate that human Tregs promote the generation of myeloid dendritic cells (DC) with reduced capacity to stimulate effector T cell responses. In a model of xenogeneic graft-versus-host disease (GVHD), allogeneic human DC conditioned with Tregs suppressed human T cell activation and completely abrogated posttransplant lethality. Tregs induced programmed death ligand-1 (PD-L1) expression on Treg-conditioned DC; subsequently, Treg-conditioned DC induced PD-L1 expression in vivo on effector T cells. PD-L1 blockade reversed Tregconditioned DC function in vitro and in vivo, thereby demonstrating that human Tregs can promote immune suppression via DC modulation through PD-L1 up-regulation. This identification of a human Treg downstream cellular effector (DC) and molecular mechanism (PD-L1) will facilitate the rational design of clinical trials to modulate alloreactivity.
Author(s): Amarnath S, Costanzo CM, Mariotti J, Ullman JL, Telford WG, Kapoor V, Riley JL, Levine BL, June CH, Fong T, Warner NL, Fowler DH
Publication type: Article
Publication status: Published
Journal: PLoS Biology
Online publication date: 02/02/2010
ISSN (print): 1544-9173
ISSN (electronic): 1545-7885
Publisher: Public Library of Science
PubMed id: 20126379
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