Immunoregulation and TGF-β 1 . Suppression of a nephritogenic murine T cell clone

Immunoregulation and TGF-β 1 . Suppression of a nephritogenic murine T cell clone. Transforming growth factor beta (TGF-β) has been clearly linked in several model systems to the development of pathologic extracellular matrix deposition in the glomerulus and interstitium. TGF-β additionally exerts multiple immunomodulatory effects on T and B lymphocytes, including growth inhibition. Such pleiotropic effects make it difficult to predict how TGF-β might directionally affect the expression of T cell mediated kidney disease. We have examined the effects of TGF-β 1 on the activity of effector T cells in a model of autoimmune interstitial nephritis. M52.26 is an antigen-specific, nephritogenic, cytotoxic T cell clone. TGF-β 1 mediates a concentration-dependent inhibition of M52.26-directed cytotoxicity of tubular epithelial cells in culture, and also of M52.26-mediated transfer of interstitial nephritis to syngeneic recipients. The loss of these functional activities is associated with distinct changes in cytokine gene expression in M52.26. These cytokine alterations consist of a loss of IFN-γ and perforin expression, and an up-regulation of TGF-β expression, which is likely relevant to the observed effector T cell inactivation.