International Immunology Advance Access published online on June 28, 2004
International Immunology, doi:10.1093/intimm/dxh107
© 2004 by The Japanese Society for Immunology
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1 Department of Pathology, College of Physicians and Surgeons of Columbia University, 630 West 168 Street, New York, NY 10032, USA
* To whom correspondence should be addressed. E-mail: ns20{at}columbia.edu.
Endothelial cells have been shown to activate T cell responses to alloantigens, triggering transplant rejection. However, they may also play a role in tolerance induction. Using RT-PCR we show here that alloantigen specific CD8+CD28- T suppressor cells generated in vitro are FOXP3 positive and interact with human endothelial cells. This interaction results in the induction of inhibitory receptors and down-regulation of costimulatory and adhesion molecules, thus rendering endothelial cells tolerogenic. In turn, tolerized endothelial cells elicit the differentiation of CD8+CD28- FOXP3+ T suppressor cells. Taken together our data demonstrate a functional and phenotypic overlap between tolerogenic dendritic cells and endothelial cells. Furthermore, alloantigen specific CD8+CD28- FOXP3+ T cells, which trigger the upregulation of inhibitory receptors in endothelial cells, are present in the circulation of heart allograft recipients in quiescence as demonstrated by flow cytometry, RT-PCR and luciferase transcription assays. Their detection facilitates the identification of patients who may benefit from partial or complete cessation of immunosuppressive therapy, a goal of obvious importance given the morbidity and mortality associated with chronic immunosuppression. Modulation of endothelial cells in favor of promoting tolerance may be important for long-term survival of organ allografts.
Accepted April 30, 2004
Article
Alloantigen specific CD8+CD28- FOXP3+ T suppressor cells induce ILT3+ ILT4+ tolerogenic endothelial cells, inhibiting alloreactivity
2 Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168 Street, New York, NY 10032, USA
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