Costimulatory markers in muscle of patients with idiopathic inflammatory myopathies and in cultured muscle cells

In an attempt to understand the mechanisms of cell injury in the inflammato ry myopathies, we analyzed the expression of costimulatory molecules, CTLA4 , CD28, CD86, CD40, and CD154 as well as HLA class I, HLA class II, and ICA M-I in normal muscle and in muscle biopsies from patients with polymyositis (PM) or dermatomyositis (DM). By immunohistochemical staining, DM and PM: biopsies showed the presence of CTLA4, CD28, CD86, and CD40 on inflammatory cells. More strikingly, however, low levels of CTLA4 and CD28 were observe d on muscle cells. The expression of CTLA4 and CD28 on nonlymphoid cells ha s not been previously reported. These unexpected findings were confirmed in cultured normal human myoblasts: various proinflammatory cytokines induced the expression of CTLA4 and CD28 on normal human muscle cells. The sequenc es of the cDNAs were found to be identical to the sequences for these molec ules in T cells. The data suggest a novel complexity in the network of cell ular interactions between the infiltrated immune cells and the muscle cells in which the normal relationship between infiltrating inflammatory cells a nd target tissue is under a previously unrecognized set of controls.