Contribution of CD8+ T cells to inflammatory cytokine production in systemic sclerosis (SSc). (16th November 2016)

• Record Type: Journal Article
• Authors: Klein, Matthias; Schmalzing, Marc; Almanzar, Giovanni; Benoit, Sandrine; Hamm, Henning; Tony, Hans-Peter; Goebeler, Matthias; Prelog, Martina
• Is Part Of: Autoimmunity. Volume 49:Number 8(2016)
• Page Start: 532
• Page End: 546
• Publication Date: 2016-11-16
• Subjects: CD8+ -- T cells -- systemic sclerosis -- cytokines -- chemokine receptors; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; 571.973
• DOI: 10.1080/08916934.2016.1217997
• Languages: English
• ISSNs: 0891-6934

Abstract

Abstract: Only limited attention has been paid to the role of CD8 + T cells in the etiopathogenesis and progression of systemic sclerosis (SSc). CD8 + T cells may have autoantigen-specific and pro-inflammatory but also immunomodulatory properties. To investigate the differentiation of CD8 + T cells, staining of cell surface factors and of chemokine receptors were performed. In addition, the cytokine-producing ability of circulating CD8 + T cells and their sensitivity to suppression by regulatory T cells (Tregs) were compared between patients with diffuse (dcSSc) or limited cutaneous SSc (lcSSc) and healthy individuals. We identified CD8 + T cells as producers of pro-inflammatory type- 2 cytokines with a significant contribution of memory CD8 + T cells. Memory CD8 + T cells of SSc patients stayed unaltered after suppression with autologous Tregs. Expression of chemokine receptors was significantly correlated with intracellular cytokine production in CD8 + T cells with a clear dichotomy of type 1 and type 2 cytokines. High levels of intracellular cytokines, such as interleukin-(IL)-4, IL-13 and tumor-necrosis-factor-alpha (TNFalpha) were positively associated with the presence of Scl-70 or anti-centromere antibodies and negatively with the administration of glucocorticoids. Administration of glucocorticoids was positively associated with higher IFNgamma production. Lack of anti-centromere antibodies and therapy with methotrexate were positively associated with higher intracellular IL-10 production. CD8 + T cells may significantly contribute to inflammation in SSc. Our findings suggest to not only focus on T helper cells in the development of therapeutic strategies but also to consider the role of CD8 + T cells in the etiopathogenesis and perpetuation of SSc.