Lymphocytes in the skin of patients with progressive systemic sclerosis

Abstract

Mononuclear cells (MNC) present in the dermis of the forearm and in the blood of patients with progressive systemic sclerosis (PSS) were quantified and analyzed for subsets using monoclonal antibodies. The findings were correlated with cutaneous and systemic features of the disease. Total T lymphocytes and their subsets, B cells, and macrophages were enumerated in the skin samples of 21 patients with PSS. The dermal MNC infiltrates consisted mostly of activated T lymphocytes with a mean T helper/T suppressor (T4/T8) ratio of 2.4 2 1.3 SD. Few B1-positive or TCpositive cells (macrophages) were observed. There was no correlation between the skin or blood T4/T8 ratios and the degree of skin thickening. On histologic examination, 58 of 115 (50%) untreated patients with PSS had prominent dermal MNC infiltration. Significant correlations between the degree of MNC infiltration and both the degree (P < 0.05) and progression (P < 0.05) of skin thickening were observed. No correlations with other systemic disease features of PSS were noted. These

Increased CD40 expression in skin fibroblasts from patients with systemic sclerosis (SSc): role of CD40‐CD154 in the phenotype of SSc fibroblasts

“…It has The ligation of CD40 in vivo relies on the presence of CD154-expressing cells in the lesional skin of SSc patients. Pathological studies have shown the infiltration of T cells [15] and mast cells [22] in lesional skin at the earliest phase of the disease. Recently, it was reported that the expression of CD154 on activated T cells in peripheral circulating lymphocytes of SSc patients is significantly increased compared to that of normal donors [23].…”

“…In an analysis of lesional skin biopsies from SSc patients, it has been reported that one of the earliest abnormalities is a collapse of vimentin intermediate filaments around the nucleus of endothelial cells [14]. Then both CD4-positive and CD8-positive T cells migrate into skin tissues [15]. Additional morphological and functional changes of fibroblasts and endothelial cells are noted coincident with the infiltration of T cells.…”

Oncostatin M Stimulates the Growth of Dermal Fibroblasts Via a Mitogen-Activated Protein Kinase-Dependent Pathway

“…Although the physiological roles of this cytokine remain largely unknown, OSM has been shown to exert a variety of effects on different types of cells. Studies have shown that fibroblasts are target cells for OSM (23,24,36,37) and that T-lymphocyte and monocyte/macrophage infiltration is observed in normal dermal repair as well as fibrotic lesions (38,39). Therefore, OSM could play a role in dermal fibrotic repair or fibrosis.…”

Effector CD8+ T cells in systemic sclerosis patients produce abnormally high levels of interleukin‐13 associated with increased skin fibrosis

“…The results of that study also showed a correlation between the reduced number of NKT cells and increased inflammation, suggesting that these cells play a regulatory role in SSc. The absolute and relative numbers of CD4ϩ T cells in SSc patients are normal, whereas those of CD8ϩ T cells are decreased (6). Since CD4ϩ T cells represent the predominant T cell infiltrate in the skin of SSc patients during the inflammatory phase of the disease and since there is a strong HLA class II major histocompatibility complex association with the autoantibody profile, clinical subsets (32,33), and T cell responses (34), most studies to date have been focused on CD4ϩ T cells.…”

“…Several lines of evidence suggest that T cells are important in the pathogenesis of SSc, including observations that ␣/␤ and ␥/␦ T lymphocytes exhibit increased expression of activation markers (3,4), show signs of antigen-driven expansion (5), and dominate the inflammatory infiltrates in the skin and involved tissues during the early stages of the disease (6,7). T cells have been found to be necessary for the production of antitopoisomerase I antibodies in SSc (8).…”