The role of cytokines in polymyositis

Objective. To investigate the effect of interferon‐γ (IFNγ) on the adhesive interactions between human peripheral blood T cells and human skeletal muscle cells at various stages of muscle cell differentiation and maturation in vitro. Methods. Human muscle cell cultures were established from normal muscle biopsy material, using the explant technique. T cells were studied for their capacity to adhere to IFNγ‐treated and untreated myoblasts and myotubes. The role of intercellular adhesion molecule type 1 (ICAM‐1) in cell adhesion to muscle cells was examined in blocking studies, by enzyme‐linked immuno‐sorbent assay (ELISA), and by immunohistochemical staining using monoclonal antibodies (MAb). Results. Treatment of muscle cells (myoblasts and myotubes) with IFNγ resulted in a significant dose‐dependent increase in the number of adherent T cells. Adhesion of T cells to muscle cells was significantly inhibited by MAb to ICAM‐1 and to lymphocyte function–associated antigen type 1, but not by MAb to HLA–DR. There was no difference in the level of T cell adhesion to IFNγ‐treated allogeneic versus autologous muscle cells. By ELISA and immunohistochemical analysis, ICAM‐1 expression on the surface of cultured human muscle cells was either absent or barely detectable, but was strongly induced by treatment of muscle cells with IFNγ. Conclusion. Induction of cell adhesion molecules on muscle cells by IFNγ may be an important mechanism for the localization of T cells in the affected muscles of patients with autoimmune myositis.