Murine vascular endothelium activates and induces the generation of allogeneic CD4+25+Foxp3+ regulatory T cells

Alexander Sasha Krupnick, Andrew E. Gelman, Winfried Barchet, Steve Richardson, Friederike H. Kreisel, Laurence A. Turka, Marco Colonna, G. Alexander Patterson, Daniel Kreisel

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

Abstract

Unlike graft-resident donor-derived hemopoietic APCs, which decrease in number over time after transplantation, vascular endothelial cells are lifelong residents of a vascularized allograft, Endothelial cells are potent APCs for allogeneic CD8+ T lymphocytes but are unable to induce proliferation of allogeneic CD4+ T lymphocytes. Although the reason for this differential response has been poorly understood, here we report that alloantigenpresentation by vascular endothelium to CD4+ T lymphocytes activates and induces CD4+25+Foxp3+ regulatory T cells, which can inhibit proliferation of alloreactive T cells both in vitro and in vivo. This process occurs independently of B7.1 costimulation but is dependent on programmed death ligand 1 (B7-H1). This finding may have important implications for tolerance induction in transplantation.

Original languageEnglish
Pages (from-to)6265-6270
Number of pages6
JournalJournal of Immunology
Volume175
Issue number10
StatePublished - Nov 15 2005

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