TY - JOUR
T1 - Interferon-β enhances monocyte and dendritic cell expression of B7-H1 (PD-L1), a strong inhibitor of autologous T-cell activation
T2 - Relevance for the immune modulatory effect in multiple sclerosis
AU - Schreiner, Bettina
AU - Mitsdoerffer, Meike
AU - Kieseier, Bernd C.
AU - Chen, Lieping
AU - Hartung, Hans Peter
AU - Weller, Michael
AU - Wiendl, Heinz
PY - 2004/10
Y1 - 2004/10
N2 - 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-β, 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-γ 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-β in vitro. Serial measurements of B7-H1 mRNA in MS patients before and 6 months after initiation of IFN-β 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-β therapy (median 1.04 vs. 8.78; p
AB - 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-β, 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-γ 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-β in vitro. Serial measurements of B7-H1 mRNA in MS patients before and 6 months after initiation of IFN-β 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-β therapy (median 1.04 vs. 8.78; p
KW - Antigen-presenting cells
KW - B7-family of costimulatory molecules
KW - B7-H1
KW - Costimulation
KW - Interferon-β
KW - Multiple sclerosis
KW - Tolerogenic cells
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UR - http://www.scopus.com/inward/citedby.url?scp=4444355857&partnerID=8YFLogxK
U2 - 10.1016/j.jneuroim.2004.06.013
DO - 10.1016/j.jneuroim.2004.06.013
M3 - Article
C2 - 15342209
AN - SCOPUS:4444355857
SN - 0165-5728
VL - 155
SP - 172
EP - 182
JO - Advances in Neuroimmunology
JF - Advances in Neuroimmunology
IS - 1-2
ER -