Article
Adhesion of cytomegalovirus-specific CD8+ T cells in systemic sclerosis
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Published: | February 5, 2019 |
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Background: The pathogenesis of systemic sclerosis (SSc) is linked to cytomegalovirus (CMV) infection, for instance through infected endothelial cells or via molecular mimicry inducing an autoimmune response. Further, in SSc endothelial damage could be mediated by adhesion of CMV-specific T cells. We hypothesize that CMV-specific CD8+ T cells display increased adhesive properties in limited and diffuse SSc, characterized by enhanced expression of CX3CR1 and activation of β2-integrins.
Methods: Peripheral blood and serum was obtained from patients with SSc (diffuse, n=10, limited, n=10) and age-and sex-matched healthy controls (HC, n=10) and checked for HLA-A*02.01 expression due to the CMVA2 nonapeptide used. Peripheral blood mononuclear cells (PBMC) from HLA-A*02.01+ SSc patients and HC were isolated using Ficoll gradient and T lymphocytes were phenotyped (CD4, CD8, CD45RA, CCR7, CX3CR1, binding of ICAM-1 multimers) by flow cytometry. Soluble fractalkine was measured by ELISA.
Results: The frequency of CMVA2-specific CD8+ T cells was increased in diffuse SSc patients in comparison to both limited SSc patients and HC. There was no difference between SSc patients and HC regarding the activation of β2-integrins by CMVA2-specific CD8+ T cells. However, the expression of CX3CR1 by CMVA2-specific CD8+ T cells was elevated in SSc patients when compared to HC. Further, in both HC and SSc patients CMVA2-specific CD8+ T cells differed from non-CMV-specific CD8+ T cells with respect to the expression of CX3CR1. In addition, the concentration of soluble fractalkine was higher in SSc when compared to HC.
Conclusion: CMV-specific CD8+ T cells show enhanced expression of the fractalkine receptor CX3CR1, likely increasing the adhesive potential of these cells to activated endothelium. Compared to HC, SSc patients showed an expansion of CMV-specific CD8+ T cells, an increase in their CX3CR1 expression and enhanced levels of soluble fractalkine, the latter indicating endothelial activation. These processed might contribute to the pathogenesis of vasculopathy in SSc and could therefore be addressed therapeutically.