Immunoregulation and TGF-beta 1. Suppression of a nephritogenic murine T cell clone.
Transforming growth factor beta (TGF-beta) has been clearly linked in several model systems to the development of pathologic extracellular matrix deposition in the glomerulus and interstitium. TGF-beta additionally exerts multiple immunomodulatory effects on T and B lymphocytes, including growth inhibition. Such pleiotropic effects make it difficult to predict how TGF-beta might directionally affect the expression of T cell mediated kidney disease. We have examined the effects of TGF-beta 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-beta 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-gamma and perforin expression, and an up-regulation of TGF-beta expression, which is likely relevant to the observed effector T cell inactivation.
Meyers
C M
CM
Department of Medicine, University of Pennsylvania, Philadelphia.
Kelly
C J
CJ
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis / Q000737:chemistry; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000473:pathology; D016219:Immunotherapy, Adoptive; D007684:Kidney Tubules / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000737:chemistry; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009395:Nephritis, Interstitial / Q000473:pathology / Q000517:prevention & control*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016207:Cytokines; D017931:DNA Primers; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016212:Transforming Growth Factor beta; D054353:Perforin