Transforming growth factor-beta 1 in experimental autoimmune neuritis. Cellular localization and time course.
Experimental autoimmune neuritis (EAN) is a monophasic inflammatory disorder 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 of Lewis rats with actively induced and adoptive transfer EAN. TGF-beta 1 mRNA was upregulated to high levels in sensory and motor roots, spinal ganglia, and sciatic nerve as revealed by quantitative Northern blot 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 revealed macrophages and subpopulations of T cells as the major cellular source of TGF-beta 1 mRNA. TGF-beta 1 protein was visualized immunocytochemically and localized to infiltrating mononuclear cells with peak expression around the same time as mRNA, in addition to some constitutive expression in axons and Schwann cells. Our studies suggest that the spontaneous recovery observed in Lewis rat EAN might be mediated by the endogenous elaboration of TGF-beta 1 within the peripheral nerve, and that macrophages might control their own cytotoxicity by expressing TGF-beta 1.
Department of Neurology, University of Würzburg, Germany.
R
R
Kiefer
K
K
Funa
T
T
Schweitzer
S
S
Jung
O
O
Bourde
K V
KV
Toyka
H P
HP
Hartung
D000818:Animals; D001327:Autoimmune Diseases; D015152:Blotting, Northern; D005260:Female; D005727:Ganglia, Spinal / Q000737:chemistry; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009443:Neuritis; D017933:Peripheral Nervous System / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000737:chemistry; D013126:Spinal Nerve Roots / Q000737:chemistry; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000032:analysis*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta