Effector CD8+ T cells in systemic sclerosis patients produce abnormally high levels of interleukin‐13 associated with increased skin fibrosis
P Fuschiotti, TA Medsger Jr… - Arthritis & Rheumatism …, 2009 - Wiley Online Library
P Fuschiotti, TA Medsger Jr, PA Morel
Arthritis & Rheumatism: Official Journal of the American College …, 2009•Wiley Online LibraryObjective T lymphocytes play an important role in systemic sclerosis (SSc), a connective
tissue disease characterized by inflammation, fibrosis, and vascular damage. While their
precise role and antigen specificity are unclear, T cell–derived cytokines likely contribute to
the induction of fibrosis. The aim of this study was to establish the role of cytokine
dysregulation by T cells in the pathogenesis of SSc. Methods To identify relationships
between a specific cytokine, T cell subset, and the disease course, we studied a large cohort …
tissue disease characterized by inflammation, fibrosis, and vascular damage. While their
precise role and antigen specificity are unclear, T cell–derived cytokines likely contribute to
the induction of fibrosis. The aim of this study was to establish the role of cytokine
dysregulation by T cells in the pathogenesis of SSc. Methods To identify relationships
between a specific cytokine, T cell subset, and the disease course, we studied a large cohort …
Objective
T lymphocytes play an important role in systemic sclerosis (SSc), a connective tissue disease characterized by inflammation, fibrosis, and vascular damage. While their precise role and antigen specificity are unclear, T cell–derived cytokines likely contribute to the induction of fibrosis. The aim of this study was to establish the role of cytokine dysregulation by T cells in the pathogenesis of SSc.
Methods
To identify relationships between a specific cytokine, T cell subset, and the disease course, we studied a large cohort of patients with diffuse cutaneous SSc (dcSSc) or limited cutaneous SSc (lcSSc). Using Luminex analysis and intracellular cytokine staining, we analyzed the intrinsic ability of CD4+ and CD8+ T cell subsets to produce cytokines following in vitro activation.
Results
High levels of the profibrotic type 2 cytokine interleukin‐13 (IL‐13) were produced following activation of peripheral blood effector CD8+ T cells from SSc patients as compared with normal controls or with patients with rheumatoid arthritis. In contrast, CD4+ T cells showed a lower and more variable level of IL‐13 production. This abnormality correlated with the extent of fibrosis and was more pronounced in dcSSc patients than in lcSSc patients.
Conclusion
Dysregulated IL‐13 production by effector CD8+ T cells is important in the pathogenesis of SSc and is critical in the predisposition to more severe forms of cutaneous disease. Our study is the first to identify a specific T cell phenotype that correlates with disease severity in SSc and can be used as a marker of immune dysfunction in SSc and as a novel therapeutic target.
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