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：2001
卷号：98
期号：5
页码：2587-2592
DOI：10.1073/pnas.051632398
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Similarities in the phenotypes of mice deficient for cytotoxic T lymphocyte antigen-4 (CTLA-4) or transforming growth factor-{beta}1 (TGF-{beta}1) and other observations have led to speculation that CTLA-4 mediates its inhibitory effect on T cell activation via costimulation of TGF-{beta} production. Here, we examine the role of TGF-{beta} in CTLA-4-mediated inhibition of T cell activation and of CTLA-4 in the regulation of TGF-{beta} production. Activation of AND TCR transgenic mouse T cells with costimulatory receptor-specific antigen presenting cells results in efficient costimulation of proliferation by CD28 ligation and inhibition by CTLA-4 ligation. Neutralizing antibody to TGF-{beta} does not reverse CTLA-4-mediated inhibition. Also, CTLA-4 ligation equally inhibits proliferation of wild-type, TGF-{beta}1-/-, and Smad3-/- T cells. Further, CTLA-4 engagement does not result in the increased production of either latent or active TGF-{beta} by CD4+ T cells. These results indicate that CTLA-4 ligation does not regulate TGF-{beta} production and that CTLA-4-mediated inhibition can occur independently of TGF-{beta}. Collectively, these data demonstrate that CTLA-4 and TGF-{beta} represent distinct mechanisms for regulation of T cell responses.
