Role of human corneal endothelial cells in T-cell-mediated alloimmune attack in vitro
Human corneal endothelial cells (HCEC) are a potential target of immune attack after corneal transplantation. The aim of this in vitro study was to investigate the role of HCEC during the alloimmune response of T-cells by examining cytokine profiles, function of the immunosuppressive enzyme indoleam...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 2014
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| In: |
Investigative ophthalmology & visual science
Year: 2014, Volume: 55, Issue: 3, Pages: 1213-1221 |
| ISSN: | 1552-5783 |
| DOI: | 10.1167/iovs.13-11930 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1167/iovs.13-11930 Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1167/iovs.13-11930 
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| Author Notes: | Imad Lahdou, Christoph Engler, Stefan Mehrle, Volker Daniel, Mahmoud Sadeghi, Gerhard Opelz, and Peter Terness |
| Summary: | Human corneal endothelial cells (HCEC) are a potential target of immune attack after corneal transplantation. The aim of this in vitro study was to investigate the role of HCEC during the alloimmune response of T-cells by examining cytokine profiles, function of the immunosuppressive enzyme indoleamine 2,3-dioxigenase (IDO), major histocompatibility complex (MHC-I/-II), T-cell proliferation, and the induction of cell death. Real-time PCR and RP-HPLC were used to determine IDO expression and activity. Multiplex assay was performed for quantification of cytokine levels. T-cell proliferation was assessed by thymidine incorporation, and HCEC cell death was measured by flow cytometry. Human corneal endothelial cells induce strong proliferation of allogeneic T-cells and an increase of proinflammatory cytokines such as interleukin-1α (IL-1α), IL-1β, IL-6, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α). Tumor necrosis factor-alpha (and to a lesser extent IFN-γ) induces apoptosis. Moreover, IFN-γ strongly upregulates MHC-II molecules and IDO activity in HCEC as reflected by high kynurenine (Kyn) concentrations. Interestingly, the T-cell response was not affected by increased IDO activity, since blocking of IDO did not affect the proliferation rate. Indoleamine 2,3-dioxigenase-induced Kyn levels did not exceed concentrations of 175 ± 20 μM. Concentrations of ≥400 μM Kyn were required to suppress T-cell proliferation. Our data show that T-cell attack on HCEC leads to increased concentrations of proinflammatory cytokines. Inflammatory cytokines induce apoptosis and upregulate MHC-II molecules and IDO in HCEC. Although increased IDO activity does not influence the T-cell response, it constitutes an inflammatory marker of the alloimmune response toward HCEC. |
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| Item Description: | Gesehen am 21.09.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1552-5783 |
| DOI: | 10.1167/iovs.13-11930 |