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

Lion, J; Burbach, M; Cross, A; Poussin, K; Taflin, C; Kaveri, S; Haziot, A; Glotz, D; Mooney, N

Journal article

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

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. Both CsA and MPA decreased HLA-DR and increased CD54 expression, whereas IVIg increased HLA-DR expression. Interleukin 6 secretion was reduced by all three immunomodulators. Preincubation of ECs with CsA or MPA limited, while IVIg amplified, Treg expansion. Because CsA, MPA, and IVIg are known for their ability to act upon leukocytes, we confirmed that ECs maintained their immunoregulatory role when allogeneic leukocytes were pretreated with CsA, MPA, or IVIg. The results reveal that individual immunosuppressors, used in the induction and maintenance of renal allograft tolerance, had direct and distinct effects on ECs. Results of experiments associating IVIg with either CsA or MPA underlined the differences observed using individual immunosuppressors. Paradoxically, CsA or MPA may increase EC mediated inflammatory responses and long-term exposure may contribute to limitation of allograft tolerance. In contrast, IVIg interaction with the endothelium may mediate some of its immunosuppressive effects through promotion of Treg expansion, contributing to the maintenance of allograft tolerance.

Publication status:: Published

Peer review status:: Peer reviewed

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Lion, J., Burbach, M., Cross, A., Poussin, K., Taflin, C., Kaveri, S., Haziot, A., Glotz, D., & Mooney, N. (2017). Endothelial Cell Amplification of Regulatory T Cells Is Differentially Modified by Immunosuppressors and Intravenous Immunoglobulin. Frontiers in Immunology, 8, 1761–1761.

MLA Style

Lion, J, et al. “Endothelial Cell Amplification of Regulatory T Cells Is Differentially Modified by Immunosuppressors and Intravenous Immunoglobulin.” Frontiers in Immunology, vol. 8, 2017, pp. 1761–61.

Chicago Style

Lion, J, M Burbach, A Cross, et al. 2017. “Endothelial Cell Amplification of Regulatory T Cells Is Differentially Modified by Immunosuppressors and Intravenous Immunoglobulin.” Frontiers in Immunology 8: 1761–61.
Print