title: Contribution of CD8+ T cells to inflammatory cytokine production in systemic sclerosis (SSc).
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.
authors: a Department of Pediatrics, Pediatric Rheumatology and Special Immunology , University Hospital Wuerzburg , Wuerzburg , Germany.
authors: Matthias
authors: M
authors: Klein
authors: b Department of Internal Medicine II, Division of Rheumatology and Clinical Immunology , University Hospital Wuerzburg , Wuerzburg , Germany , and.
authors: Marc
authors: M
authors: Schmalzing
authors: a Department of Pediatrics, Pediatric Rheumatology and Special Immunology , University Hospital Wuerzburg , Wuerzburg , Germany.
authors: Giovanni
authors: G
authors: Almanzar
authors: c Department of Dermatology, Venereology and Allergology , University Hospital Wuerzburg , Wuerzburg , Germany.
authors: Sandrine
authors: S
authors: Benoit
authors: c Department of Dermatology, Venereology and Allergology , University Hospital Wuerzburg , Wuerzburg , Germany.
authors: Henning
authors: H
authors: Hamm
authors: b Department of Internal Medicine II, Division of Rheumatology and Clinical Immunology , University Hospital Wuerzburg , Wuerzburg , Germany , and.
authors: Hans-Peter
authors: HP
authors: Tony
authors: c Department of Dermatology, Venereology and Allergology , University Hospital Wuerzburg , Wuerzburg , Germany.
authors: Matthias
authors: M
authors: Goebeler
authors: a Department of Pediatrics, Pediatric Rheumatology and Special Immunology , University Hospital Wuerzburg , Wuerzburg , Germany.
authors: Martina
authors: M
authors: Prelog
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D019707:Receptors, Chemokine
keywords: CD8+; T cells; chemokine receptors; cytokines; systemic sclerosis