Interferon-beta enhances monocyte and dendritic cell expression of B7-H1 (PD-L1), a strong inhibitor of autologous T-cell activation: relevance for the immune modulatory effect in multiple sclerosis - PubMed (original) (raw)

Interferon-beta enhances monocyte and dendritic cell expression of B7-H1 (PD-L1), a strong inhibitor of autologous T-cell activation: relevance for the immune modulatory effect in multiple sclerosis

Bettina Schreiner et al. J Neuroimmunol. 2004 Oct.

Abstract

Antigen-presenting cells (APC) are considered to play a critical role in promoting the (re)activation of potentially autoreactive T cells in multiple sclerosis (MS), an inflammatory demyelinating disorder of the central nervous system (CNS). B7-H1 (PD-L1) is a novel member of the B7 family proteins which exert costimulatory and immune regulatory functions. Here we characterize the expression and functional activity of B7-H1 expressed on monocytes and dendritic cells (DC) of healthy donors and MS patients. B7-H1 is constitutively expressed on monocytes and differentially matured DC, but not on B cells. IFN-beta, the principle immune modulatory agent used for the treatment of MS, strongly enhances B7-H1 expression on monocytes and semi-matured DC, but not B cells, in vitro. Importantly, B7-H1 expressed on APC strongly inhibits autologous CD4 T-cell activation. Neutralization of B7-H1 on monocytes or differentially matured monocyte-derived DC markedly increases the secretion of the pro-inflammatory cytokines, IFN-gamma and IL-2, T-cell proliferation, and the expression of T-cell activation markers. B7-H1 exhibits strong inhibitory effects when expressed on monocytes, immature or semi-mature DC, but less so when expressed on fully matured DC. B7-H1-dependent immune inhibition is in part mediated by CD4/CD25+ regulatory T cells. There is no difference in the baseline expression levels of monocytic B7-H1 between untreated MS patients and healthy donors. However, both groups show a significant concentration-dependent up-regulation of B7-H1 mRNA and protein in response to IFN-beta in vitro. Serial measurements of B7-H1 mRNA in MS patients before and 6 months after initiation of IFN-beta therapy corroborated the relevance of these results in vivo: Nine of nine patients showed a significant increase in B7-H1 mRNA levels after 6 months of IFN-beta therapy (median 1.04 vs. 8.78; p<0.05, two-sided t-test). Accordingly, protein expression of B7-H1 on monocytes was up-regulated after 24 h of IFN-beta application. In summary, B7-H1 expressed on APC acts as a strong inhibitor of autologous CD4 T-cell activation and may thus contribute to the maintenance of peripheral immune tolerance. IFN-beta up-regulates B7-H1 in vitro and in MS patients in vivo and might represent a novel mechanism how IFN-beta acts as a negative modulator on APC T-cell interactions in the periphery.

PubMed Disclaimer

Cited by

Immune checkpoints in central nervous system autoimmunity.
Joller N, Peters A, Anderson AC, Kuchroo VK. Joller N, et al. Immunol Rev. 2012 Jul;248(1):122-39. doi: 10.1111/j.1600-065X.2012.01136.x. Immunol Rev. 2012. PMID: 22725958 Free PMC article. Review.
High PD-L1/CD274 Expression of Monocytes and Blood Dendritic Cells Is a Risk Factor in Lung Cancer Patients Undergoing Treatment with PD1 Inhibitor Therapy.
Riemann D, Schütte W, Turzer S, Seliger B, Möller M. Riemann D, et al. Cancers (Basel). 2020 Oct 13;12(10):2966. doi: 10.3390/cancers12102966. Cancers (Basel). 2020. PMID: 33066260 Free PMC article.
The DC-HIL/syndecan-4 pathway inhibits human allogeneic T-cell responses.
Chung JS, Bonkobara M, Tomihari M, Cruz PD Jr, Ariizumi K. Chung JS, et al. Eur J Immunol. 2009 Apr;39(4):965-74. doi: 10.1002/eji.200838990. Eur J Immunol. 2009. PMID: 19350579 Free PMC article.
Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma.
Zeng Z, Shi F, Zhou L, Zhang MN, Chen Y, Chang XJ, Lu YY, Bai WL, Qu JH, Wang CP, Wang H, Lou M, Wang FS, Lv JY, Yang YP. Zeng Z, et al. PLoS One. 2011;6(9):e23621. doi: 10.1371/journal.pone.0023621. Epub 2011 Sep 1. PLoS One. 2011. PMID: 21912640 Free PMC article.
Dendritic cell-derived exosomes for cancer immunotherapy: hope and challenges.
Tian H, Li W. Tian H, et al. Ann Transl Med. 2017 May;5(10):221. doi: 10.21037/atm.2017.02.23. Ann Transl Med. 2017. PMID: 28603736 Free PMC article. No abstract available.

Interferon-beta enhances monocyte and dendritic cell expression of B7-H1 (PD-L1), a strong inhibitor of autologous T-cell activation: relevance for the immune modulatory effect in multiple sclerosis - PubMed (original) (raw)