Background Fibrotic skin changes in systemic sclerosis (SSc) and allied conditions characteristically are preceded by an inflammatory infiltrate rich in T cells. It is not known whether recruited T cells induce fibrosis or react to developing fibrosis.
Objectives Chemokines (CC) are involved in cell recruitment into inflammatory sites. Our aim was to characterise the CC receptor (R) usage as well as the effector function of T cells infiltrating a developing fibrotic skin lesion in a SLE patient.
Methods T cells from a lesional skin biopsy were grown in vitro in the presence of IL-2. TcR, accessory molecules, and CCR expression were analysed by flow cytometry and RNase protection assay. The capacity to release interferon-g (IFN-g) and IL-4 was assessed upon CD3-crosslinking in phenotypically homogeneous T cell lines or clones. The chemotactic responses to synthetic CC was assessed. Immunohistochemistry was performed on the same tissue.
Results T cells infiltrating the affected skin were heterogeneous in terms of accessory molecules (CD4+, CD8+, and CD4CD8 double negative) as well as of TcR (a/b and g/d) expression. The majority preferentially produced IFN-g, while a minority produced both IFN-g and IL-4. Preferential expression of type-1-related CXCR3 (and response to relevant CC) was observed and confirmed by tissue immunohistochemistry. Interestingly, several T cells coexpressed type 1 and type 2-related CCR and migrated to an equivalent extent in response to specific ligands.
Conclusion The analysis performed on T cells infiltrating a novel fibrotic skin lesion from a SLE patient has revealed heterogeneous expression of CC receptors by T cells preferentially producing IFN-gamma. Since IFN-gamma exerts a potent inhibitory activity on ECM deposition by fibroblasts, these results hint to a reactive mechanisms aimed to control the extent of fibrosis.
Chizzolini C, Rezzonico R, Ribbens C, Burger D, Wollheim FA, Dayer J-M. Inhibition of type I collagen production by dermal fibroblasts upon contact with activated T cells. Different sensitivity to inhibition of systemic sclerosis and control fibroblasts. Arthitis Rheum. 1998;41:2039–47
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