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Ping Chen, Lai Wei, Baoying Liu, Tiaojiang Xiao, Sima Hirani, Zhiyu Li, Shayma Jawad, Richard W J Lee, H Nida Sen, Robert B Nussenblatt; Increased Blood CD1c(high) Myeloid Dendritic Cells with Low Antigen Uptake Enhance CD4 Helper T cell Responses in Noninfectious Uveitis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4062.
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© ARVO (1962-2015); The Authors (2016-present)
Myeloid dendritic cells (mDCs) initiate CD4+ T cell immune responses after taking up and presenting self-antigens to T cells, which have been implicated in the pathogenesis of autoimmune disease. To elucidate this biological event, the present study investigated the role of Lineage1-HLADR+ CD1c+ myeloid dendritic cells 1 (mDC1) in T cell mediated immune responses in noninfectious uveitis.
Peripheral blood from noninfectious uveitis patients (n=92) and healthy controls (HCs, n=112) was analyzed. Lineage 1-HLA-DR+CD1c+ mDC1 were identified by flow cytometry. Monocyte-derived DCs (MoDCs) were also generated from uveitis patients and HCs by culturing isolated CD14+ cells for 6 days with GM-CSF and interleukin (IL)-4. The capacity of DCs to process antigen and respond to lipopolysaccharide (LPS) was then quantified by measuring FITC-labeled albumin uptake, intracellular cytokine expression and co-cultured CD4+ T cell proliferation.
Flow cytometric analysis revealed a significant increase in CD1c+ mDC1 in the peripheral blood of uveitis patients as compared to HCs. The increased CD1c+ mDC1 were characterized by high expression of HLADR and low antigen uptake, indicating blood mDC1 maturation in patients. mDC1 was separated into two subpopulations as CD1c(high) mDC1 and CD1c(low) mDC1. CD1c(high) mDC1 had higher HLADR expression and lower antigen uptake as compared to that observed in CD1c(low) mDC1. Importantly, the percentage of CD1c(high) mDC1 was increased in uveitis patients. Monocyte-derived DCs (MoDCs), one of the sources of mDCs, were sorted into two populations based on their capability of antigen uptake. MoDCs with lower antigen uptake and higher CD1c expression induced more CD4+ T helper cell activation and proliferation as compared to the MoDCs exhibiting higher antigen uptake and low CD1c expression. The results demonstrate that CD1c+ mDC1, in particular the CD1c(high) mDC1 subpopulation, have low antigen uptake but enhance T cell immune responses in uveitis patients.
Together, our results reveal that the function and phenotype of blood CD1c+ mDC1 are altered in the circulation of noninfectious uveitis patients prior to entering eye tissue or draining lymph nodes, which adds to our understanding of the mechanism of uveitis, and may have broader implications to autoimmune disease in general.
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