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 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-beta 1 (TGF-beta 1) on the clinical signs, histological changes, cell-mediated immune responses, and secretion of interferon-gamma (IFN-gamma) by lymphoid cells of rats with EAN were examined. Systemic administration of TGF-beta 1 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-gamma. The profound effect of TGF-beta on disease progression in EAN, a T-cell-mediated process, is consistent with a direct effect of this growth factor on T lymphocytes.
Gregorian
S K
SK
Department of Immunology, Genentech, South San Francisco, California 94080.
Lee
W P
WP
Beck
L S
LS
Rostami
A
A
Amento
E P
EP
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology; D018996:Myelin P2 Protein; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007376:Interleukin-2; D004676:Myelin Basic Protein; D018996:Myelin P2 Protein; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; C076290:myelin P2 peptide SP26; D007371:Interferon-gamma