[The role of extracellular matrix components in the T-cell activation in systemic sclerosis]

Patients with systemic sclerosis (SSc) show, in addition to tissue fibrosis, a variety of distinct vascular and immunological abnormalities. Extracellular matrix proteins (ECM) play an important role in the regulation of cell migration and expression of various genes involved in activation of immune reactions. The aim of our study was to examine the co-stimulatory effects of ECM components (type I and IV collagen, laminin, fibronectin) in patients with SSc and to examine the expression of beta 1-integrins (VLA-2/CD49b, VLA-3/CD49c and VLA-5/CD49e) on PBMC in these patients. We examined 66 patients with various types of SSc and 62 healthy volunteers. The results showed that fibronectin and type I collagen had the highest co-stimulatory activities in both SSc patients and controls, whereas laminin and type IV collagen were less potent co-stimulatory agents. Flow cytometry data showed an increased expression of integrins (VLA-2, VLA-3, VLA-5) in SSc T-cells in comparison to healthy volunteers. The results of the proliferation assays in patients with SSc and normal volunteers showed that only fibronectin stimulated CD3--dependent lymphocyte response. Fibronectin co-stimulated T-cell proliferation in patients with SSc which may be dependent on increased expression of integrins CD49c or CD49e or/and level of circulating T-cells bearing these markers. Increasing of the expression of integrins on PBMC can help their migration to the perivascular spaces and can stimulate them. Fibronectin could enhance activation of PBMC followed by production of some cytokines involved in fibrosis in SSc.