Endothelial Cell Amplification of Regulatory T Cells Is Differentially Modified by Immunosuppressors and Intravenous Immunoglobulin

Frontiers in Immunology
Julien LionNuala Mooney

Abstract

Immunosuppressive treatment is a prerequisite for both organ transplantation and tolerance of the allograft. However, long-term immunosuppression has been associated with a higher incidence of malignancies and infections. Immunosuppressors mainly target circulating immune cells and little is known of their "off-target" effects, such as their impact on endothelial cells (ECs). In chronic antibody-mediated rejection (AMR), the allograft endothelium is a target of damage, histologically detected as transplant glomerulopathy, and which correlates with poor graft survival. Under inflammatory conditions, EC expression of HLA class II antigens can lead to CD4+-T lymphocyte alloactivation and selective expansion of pro-inflammatory Th17 and pro-tolerance Treg subsets. This response can be modified and preactivation of the EC by HLA-DR antibody binding promoted a proinflammatory Th17 response. However, whether or not immunosuppressors alter EC immunogenicity has not been examined. In alloimmunized patients with AMR, cyclosporine A (CsA) and mycophenolic acid (MPA) are often combined with intravenous immunoglobulins (IVIgs). This study reports changes in the microvascular EC phenotype and function after treatment with CsA, MPA, or IVIg. ...Continue Reading

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Citations

Apr 29, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Anat R TamburPeter Nickerson
Feb 13, 2018·Frontiers in Immunology·Amy Rachael CrossNuala Mooney
Oct 10, 2020·Biochemical and Biophysical Research Communications·Wei HuangYuanhua Huang
Apr 9, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nicolas DegauqueNuala Mooney
Jul 27, 2021·Frontiers in Immunology·Amy Rachael CrossNuala Mooney
Oct 13, 2021·Immunity, Inflammation and Disease·Stéphanie PonsLara Zafrani

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Methods Mentioned

BETA
nuclear translocation
flow cytometry
PCR
Assay
FACS
Enzyme-linked
enzyme-linked immunosorbent assay

Software Mentioned

GraphPad Prism

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American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
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