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Platelet-derived or soluble CD154 induces vascularized allograft rejection independent of cell-bound CD154
He Xu, … , Roslyn B. Mannon, Allan D. Kirk
He Xu, … , Roslyn B. Mannon, Allan D. Kirk
Published March 1, 2006
Citation Information: J Clin Invest. 2006;116(3):769-774. https://doi.org/10.1172/JCI27155.
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Research Article Immunology

Platelet-derived or soluble CD154 induces vascularized allograft rejection independent of cell-bound CD154

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Abstract

CD154 is a cell surface molecule expressed on activated T cells that binds to CD40, an activating molecule on APCs. Its blockade has been shown to prevent allograft rejection, presumably by interrupting interactions between T cells and APCs. It is known that activated human platelets express and shed CD154 and can induce APC activation and other immune processes in vitro. Here we show that platelet-derived CD154 is sufficient to initiate cardiac allograft rejection independent of any cellular source of this molecule. CD154-KO mice reject cardiac allografts after receiving CD154-expressing human platelets or recombinant CD154 (rCD154) trimers. Treatment with the human CD154-specific mAb 5c8 specifically prevents this induced rejection. Soluble trimers, but not platelets, induce rejection when infused temporally remote from the surgical procedure, suggesting that surgically induced platelet activation is required for CD154 release. Allograft rejection can thus be instigated by activated platelets through CD154. These data implicate platelets as a proximal component of acquired alloimmunity, providing insight into the mechanisms of allograft rejection and the physiological response to trauma in general.

Authors

He Xu, Xiaojie Zhang, Roslyn B. Mannon, Allan D. Kirk

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Figure 1

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Human CD154 (hCD154) induces cellular proliferation in mice that is bloc...
Human CD154 (hCD154) induces cellular proliferation in mice that is blocked by human CD154–specific but not murine CD154–specific antibodies. Shown are results from MLR using B6-CD154-KO responders (B6.129S2-Tnfsf5) versus BALB/c stimulators with or without human rCD154 trimers (50 μg/ml) and/or the human- or murine-specific CD154 mAbs. KO lymphocytes respond poorly in MLRs, and this response is greatly augmented by the addition of human CD154 trimers. This proliferation is specifically blocked by the human-specific antibody 5c8 but not by the murine-specific antibody MR-1 or isotype controls.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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