期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：21
页码：12516-12521
DOI：10.1073/pnas.95.21.12516
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：A myelin basic protein (MBP)-specific BALB/c T helper 1 (Th1) clone was transduced with cDNA for murine latent transforming growth factor-{beta}1 (TGF-{beta}1) by coculture with fibroblasts producing a genetically engineered retrovirus. When SJL x BALB/c F1 mice, immunized 12-15 days earlier with proteolipid protein in complete Freund's adjuvant, were injected with 3 x 106 cells from MBP-activated untransduced cloned Th1 cells, the severity of experimental allergic encephalomyelitis (EAE) was slightly increased. In contrast, MBP-activated (but not resting) latent TGF-{beta}1-transduced T cells significantly delayed and ameliorated EAE development. This protective effect was negated by simultaneously injected anti-TGF-{beta}1. The transduced cells secreted 2-4 ng/ml of latent TGF-{beta}1 into their culture medium, whereas control cells secreted barely detectable amounts. mRNA profiles for tumor necrosis factor, lymphotoxin, and interferon-{gamma} were similar before and after transduction; interleukin-4 and -10 were absent. TGF-{beta}1-transduced and antigen-activated BALB/c Th1 clones, specific for hemocyanin or ovalbumin, did not ameliorate EAE. Spinal cords from mice, taken 12 days after receiving TGF-{beta}1-transduced, antigen-activated cells, contained detectable amounts of TGF-{beta}1 cDNA. We conclude that latent TGF-{beta}1-transduced, self-reactive T cell clones may be useful in the therapy of autoimmune diseases.
