FRI0208 Coexpression of th1 and th2-associated chemokine receptors in t cells infiltrating early fibrotic skin in a sle patient. (1st June 2001)

• Record Type: Journal Article
• Authors: Chizzolini, C; Hess, M; Uguccioni, MG; Baggiolini, M; Dayer, JM; Loetscher, P
• Is Part Of: Annals of the rheumatic diseases. Volume 60(2001)Supplement 1
• Page Start: A115
• Page End: A116
• Publication Date: 2001-06-01
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2001.289
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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. Reference: 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