TRANSFORMING GROWTH-FACTOR-BETA-1 IN EXPERIMENTAL AUTOIMMUNE NEURITIS- CELLULAR LOCALIZATION AND TIME COURSE

Experimental autoimmune neuritis (EAN) is a monophasic inflammatory di sorder of the peripheral nervous system that resolves spontaneously by molecular mechanisms as yet unknown We have investigated whether the immunosuppressive cytokine transforming growth factor-beta 1 (TGF-beta 1) might be endogenously expressed in the peripheral nervous system o f Lewis rats with actively induced and adoptive transfer EAN. TGF-beta 1 mRNA was upregulated to high levels in sensory and motor roots, spi nal ganglia, and sciatic nerve as revealed by quantitative Northern bl ot analysis and in situ hybridization histochemistry, with peak levels just preceding the first signs of clinical recovery. TGF-beta 1 mRNA was localized to scattered round cells and dense cellular infiltrates, but only rarely to Schwann cell profiles. Double labeling studies rev ealed macrophages and subpopulations of T cells as the major cellular source of TGF-beta 1 mRNA. TGF-beta 1 protein teas visualized immunocy tochemically and localized to infiltrating mononuclear cells with peak , expression around the same time as mRNA, in addition to some constit utive expression in axons and Schwann cells, Our studies suggest that the spontaneous recovery observed in Lewis rat EAN might be mediated b y the endogenous elaboration of TGF-beta 1 within the peripheral nerve , and that macrophages might control their own cytotoxicity by express ing TGF-beta 1.