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Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan
In polymyositis (PM)/dermatomyositis (DM), T cells infiltrate the
muscle tissues and interact with muscle cells via cell surface
molecules. Recently, myoblasts have been reported to express CD40, but
little is known about the role of CD40 in myoblasts. In the present
study we examined the expression and involvement of CD40 and CD40
ligand (CD40L) in the interaction between muscle cells and T cells in
PM/DM. Immunohistochemical staining revealed that CD40 was expressed on
muscle cells in five of five PM and four of five DM patients, and that
infiltrating mononuclear cells (MNCs) expressed CD40L in all cases of
PM/DM. These CD40L-expressing MNCs were primarily CD4+ T
cells. IFN-
, which is known to induce CD40 expression on various
types of cells, was also expressed on the MNCs in four of the PM and
four of the DM patients. Although cultured human myoblasts (SkMC 2859)
did not express CD40 constitutively, IFN- induced CD40 expression in
a dose-dependent manner. To clarify the functional roles of
CD40-mediated signals, the effects of a trimeric form of recombinant
human CD40L on cytokine production were studied in SkMC 2859 that were
prestimulated with IFN- to express CD40. Recombinant human CD40L
markedly increased the production of IL-6, IL-8, IL-15, and monocyte
chemoattractant protein-1 of SkMC 2859. The expression of these humoral
factors in muscle cells of PM and DM was demonstrated by
immunohistochemistry. These results suggest that interaction between T
cells and muscle cells via the CD40-CD40L system contributes to the
immunopathogenesis of PM/DM by augmenting inflammation via cytokine
production by the muscle cells.
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