OBJECTIVE: Fibrotic skin changes in systemic sclerosis (SSc) are preceded by the appearance of an inflammatory infiltrate rich in T cells. Since no direct comparison with T cells in normal skin has been performed previously, this study was undertaken to functionally characterize T cells in the skin of patients with early active SSc and in normal skin. METHODS: We characterized coreceptor expression, T cell receptor (TCR) usage, cytokine production, and helper and cytolytic activity of T cell lines and clones established from skin biopsy specimens from 6 SSc patients and 4 healthy individuals. Immunofluorescence analysis of skin biopsy and peripheral blood samples was performed to confirm the presence of specific subsets in vivo. RESULTS: A distinct subset expressing both CD4 and CD8alpha/beta coreceptors at high levels (double-positive [DP]) was present in T cell lines from SSc and normal skin. DP T cells actively transcribed both accessory molecules, exerted clonally distributed cytolytic and helper activity, and expressed TCR clonotypes distinct from those in CD4+ or CD8+ single-positive (SP) T cells. In SSc skin, DP T cells produced very high levels of interleukin-4 (IL-4) compared with CD4+ SP T cells. Furthermore, DP T cells were directly identified in SSc skin, thus providing evidence that they are a distinct subset in vivo. CONCLUSION: The present findings show that T cells with the unusual CD4+CD8+ DP phenotype are present in the skin. Their very high level of IL-4 production in early active SSc may contribute to enhanced extracellular matrix deposition by fibroblasts.
OBJECTIVE:Fibrotic skin changes in systemic sclerosis (SSc) are preceded by the appearance of an inflammatory infiltrate rich in T cells. Since no direct comparison with T cells in normal skin has been performed previously, this study was undertaken to functionally characterize T cells in the skin of patients with early active SSc and in normal skin. METHODS: We characterized coreceptor expression, T cell receptor (TCR) usage, cytokine production, and helper and cytolytic activity of T cell lines and clones established from skin biopsy specimens from 6 SSc patients and 4 healthy individuals. Immunofluorescence analysis of skin biopsy and peripheral blood samples was performed to confirm the presence of specific subsets in vivo. RESULTS: A distinct subset expressing both CD4 and CD8alpha/beta coreceptors at high levels (double-positive [DP]) was present in T cell lines from SSc and normal skin. DP T cells actively transcribed both accessory molecules, exerted clonally distributed cytolytic and helper activity, and expressed TCR clonotypes distinct from those in CD4+ or CD8+ single-positive (SP) T cells. In SSc skin, DP T cells produced very high levels of interleukin-4 (IL-4) compared with CD4+ SP T cells. Furthermore, DP T cells were directly identified in SSc skin, thus providing evidence that they are a distinct subset in vivo. CONCLUSION: The present findings show that T cells with the unusual CD4+CD8+ DP phenotype are present in the skin. Their very high level of IL-4 production in early active SSc may contribute to enhanced extracellular matrix deposition by fibroblasts.
Authors: Britta C Martel; Beatrice Dyring-Andersen; Lone Skov; Kristian Thestrup-Pedersen; Søren Skov; Kresten Skak; Lars K Poulsen Journal: Inflamm Res Date: 2015-12-31 Impact factor: 4.575
Authors: Debendra Pattanaik; Monica Brown; Bradley C Postlethwaite; Arnold E Postlethwaite Journal: Front Immunol Date: 2015-06-08 Impact factor: 7.561
Authors: Kathryn S Torok; Katherine Kurzinski; Christina Kelsey; Jonathan Yabes; Kelsey Magee; Abbe N Vallejo; Thomas Medsger; Carol A Feghali-Bostwick Journal: Semin Arthritis Rheum Date: 2015-06-17 Impact factor: 5.532