%0 Journal Article
%T Characterisation of the immune response to type I collagen in scleroderma
%A Kenneth J Warrington
%A Usha Nair
%A Laura D Carbone
%A Andrew H Kang
%A Arnold E Postlethwaite
%J Arthritis Research & Therapy
%D 2006
%I BioMed Central
%R 10.1186/ar2025
%X Systemic sclerosis (scleroderma) (SSc) is characterised by immune activation, microvascular dysfunction, and progressive fibrosis. Increased deposition of type I collagen (CI) is evident in the skin and involved internal organs of patients with SSc [1].Cellular components and soluble mediators of the adaptive immune system play a central role in disease pathogenesis [2]. Activated T cells and levels of soluble interleukin (IL)-2 receptor are increased in the peripheral blood of patients with SSc [3-5]. In the skin, cellular infiltration precedes dermal fibrosis and consists of activated T lymphocytes, plasma cells, and macrophages [6,7]. Helper (CD4) T cells predominate, and the degree of cellular infiltration correlates with both the degree and progression of skin thickening [8]. Memory T cells are also present in the inflammatory infiltrate of affected internal organs, such as the lungs [9].There is evidence to suggest that the activation of T cells in SSc is antigen-driven [10]. Analysis of the T-cell receptor repertoire in skin biopsies of patients with SSc revealed that T cells have undergone clonal expansion. Indeed, the presence of a dominant T-cell clone in skin biopsies obtained from a patient at different time points and from different skin regions implies that the putative driving antigen is persistently present and widely distributed [11].Putative antigens in SSc include DNA topoisomerase I, RNA polymerases, and microbial products. CI has also been implicated as an autoantigen in SSc, and several reports suggest that patients with SSc exhibit cellular immunity to CI [12-14]. Peripheral blood mononuclear cells (PBMCs) from the majority of patients produce chemotactic cytokines when cultured with CI [12]. CI-stimulated PBMCs from patients with SSc produce IL-6 [13] and IL-2; the latter is predominantly derived from CD4+, but not CD8+, T cells [14]. McKown et al. reported that PBMCs from most patients with SSc produce IFN-¦Ã, IL-10, or both when cultured wit
%U http://arthritis-research.com/content/8/4/R136