Regulation of experimental autoimmune neuritis by transforming growth factor-β1

Abstract

Experimental autoimmune neuritis (EAN) is a T-cell-mediated autoimmune disease characterized by demyelination and mononuclear cell infiltration of the peripheral nervous system. It is induced in Lewis rats by administration of myelin P2 protein or a synthetic peptide (SP-26) corresponding to amino acid residues 53-78 of bovine P2 protein. The effects of transforming growth factor-β1 (TGF-β1) on the clinical signs, histological changes, cell- mediated immune responses, and secretion of interferon-γ (IFN-γ) by lymphoid cells of rats with EAN were examined. Systemic administration of TGF-β1 markedly inhibited the clinical signs and histological changes of EAN when given intraperitoneally every other day for Days 0 through 18. In addition, it decreased proliferative responses and reduced the delayed-type hypersensitivity (DTH) response to SP-26 compared to control rats. The reduction in clinical severity correlated with skin test unresponsiveness (DTH) to the disease-inducing agent (SP-26) as well to decreased cellular responsiveness to the antigen in vitro. The decrease in cellular responsiveness extended to a decrease in at least one T cell lymphokine, IFN- γ. The profound effect of TGF-β on disease progression in EAN, a T-cell- mediated process, is consistent with a direct effect of this growth factor on T lymphocytes. © 1994 Academic Press Inc.