Nature of the mononuclear infiltrate and the mechanism of muscle damage in juvenile dermatomyositis and Duchenne muscular dystrophy

Abstract

Normal skeletal muscle does not express class I MHC antigens. In contrast, these antigens are strongly expressed at the periphery of muscle fibres in patients with juvenile dermatomyositis (JDM) and Duchenne muscular dystrophy (DMD). Interferons can induce the expression of class I antigens, but in this study interferon-γ could not be detected in JDM muscle biopsy specimens using four different immunocytochemical techniques. However, an infiltrate of mononuclear cells capable of synthesising interferons was present in biopsies from JDM and DMD patients. The predominant cell types detected in both diseases were macrophages and T lymphocytes, these two cell types comprising more than 80% of the infiltrating mononuclear cells. A striking predominance of CD4 + helper/inducer T cells was observed. The majority of these cells expressed class II MHC antigens and were, therefore, considered to be activated. Additional evidence for the functional activity of CD4 + T cells was derived from the finding that it was this population of cells from JDM biopsies which proliferated in response to interleukin-2 in vitro. T cell subsets in peripheral blood were also investigated in JDM and DMD patients. Only in the case of JDM were any significant differences from normal observed, where a significant reduction in the number of peripheral blood CD8 + T cells resulted in an elevation of CD4 +/CD/8 + ratios. The role of CD4 + T cells and aberrant class I MHC antigen expression in mediating muscle damage in JDM and DMD is discussed.