REGULATION OF EXPERIMENTAL AUTOIMMUNE NEURITIS BY TRANSFORMING GROWTH-FACTOR-BETA-1

Experimental autoimmune neuritis (EAN) is a T-cell-mediated autoimmune disease characterized by demyelination and mononuclear cell infiltrat ion of the peripheral nervous system. It is induced in Lewis rats by a dministration of myelin P-2 protein or a synthetic peptide (SP-26) cor responding to amino acid residues 53-78 of bovine P-2 protein. The eff ects of transforming growth factor-beta 1 (TGF-beta 1) on the clinical signs, histological changes, cell-mediated immune responses, and secr etion of interferon-gamma (IFN-gamma) by lymphoid cells of rats with E AN were examined. Systemic administration of TGF-beta 1 markedly inhib ited the clinical signs and histological changes of EAN when given int raperitoneally every other day for Days 0 through 18. In addition, it decreased proliferative responses and reduced the delayed-type hyperse nsitivity (DTH) response to SP-26 compared to control rats. The reduct ion in clinical severity correlated with skin test unresponsiveness (D TH) to the disease-inducing agent (SP-26) as well to decreased cellula r responsiveness to the antigen in vitro. The decrease in cellular res ponsiveness extended to a decrease in at least one T cell lymphokine, IFN-gamma. The profound effect of TGF-beta on disease progression in E AN, a T-cell-mediated process, is consistent with a direct effect of t his growth factor on T lymphocytes. (C) 1994 Academic Press, Inc.