Transplantation of Systemic Sclerosis (SSc) Skin Grafts into Severe Combined Immunodef icient Mice: Increased Presence of SSc Leukocytes in SSc Skin Grafts and Autoantibody Production following Autologous Leukocyte Transfer

Abstract

This study was performed to evaluate the potential of the severe combined immunodeficient (Scid) mouse as a model to study the pathogenesis of systemic sclerosis (SSc). Scid mice were divided into three treatment groups: group 1 received skin grafts and autologous peripheral blood mononuclear cells (PBMC) from either SSc patients or normal individuals, group 2 received only SSc or normal skin grafts, and group 3 received only SSc or normal PBMC transfer. Antinuclear antibodies with a similar expression pattern as in the donor patients were detected in SSc-Scid group 1. Increased numbers of human PBMC were detected after autologous PBMC transfer in normal or SSc skin grafts without crossover into the adjacent mouse tissue. The CD4/ CD8 ratio in these infiltrates was ∼ 1.0. Although SSc skin transplantations and autologous PBMC transfer into Scid mice did not reproduce the inflammatory events found in the original SSc skin biopsies, these mice could be useful to study the expression of SSc-specific autoantibodies.

Molecular Subsets in the Gene Expression Signatures of Scleroderma Skin

“…Previous studies have identified infiltrating T cells in the skin of dSSc patients [19], [20], [21], [22], [23], although an association between T cell gene expression and dSSc was not observed in our prior study [16]. A new result from this study is genes typically associated with T cells are more highly expressed in a subset of the patients ( Figure 1F ).…”