ROLE OF CYTOKINES IN POLYMYOSITIS .3. RECOMBINANT HUMAN INTERFERON-GAMMA ENHANCES T-CELL ADHESION TO CULTURED HUMAN MUSCLE-CELLS

Objective. To investigate the effect of interferon-gamma (IFN gamma) o n the adhesive interactions between human peripheral blood T cells and human skeletal muscle cells at various stages of muscle cell differen tiation 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 IFN g amma-treated and untreated myoblasts and myotubes. The role of interce llular adhesion molecule type 1 (ICAM-1) in cell adhesion to muscle ce lls was examined in blocking studies, by enzyme-linked immunosorbent a ssay (ELISA), and by immunohistochemical staining using monoclonal ant ibodies (MAb). Results. Treatment of muscle cells (myoblasts and myotu bes) with IFN gamma 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 functi on-associated antigen type 1, but not by MAb to HLA-DR. There was no d ifference in the level of T cell adhesion to IFN gamma-treated allogen eic versus autologous muscle cells. By ELISA and immunohistochemical a nalysis, ICAM-1 expression on the surface of cultured human muscle cel ls was either absent or barely detectable, but was strongly induced by treatment of muscle cells with IFN gamma. Conclusion. induction of ce ll adhesion molecules on muscle cells by IFN gamma may be an important mechanism for the localization of T cells in the affected muscles of patients with autoimmune myositis.