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

被引:21
作者
GREGORIAN, SK
LEE, WP
BECK, LS
ROSTAMI, A
AMENTO, EP
机构
[1] STANFORD UNIV,SCH MED,DEPT DERMATOL,STANFORD,CA 94305
[2] GENENTECH INC,DEPT IMMUNOL,S SAN FRANCISCO,CA 94080
[3] UNIV PENN,SCH MED,DEPT NEUROL,IMMUNOL GRAD GRP,PHILADELPHIA,PA 19104
关键词
D O I
10.1006/cimm.1994.1156
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 P-2 protein or a synthetic peptide (SP-26) corresponding to amino acid residues 53-78 of bovine P-2 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. (C) 1994 Academic Press, Inc.
引用
收藏
页码:102 / 112
页数:11
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