| Literature DB >> 11226283 |
T J Sullivan1, J J Letterio, A van Elsas, M Mamura, J van Amelsfort, S Sharpe, B Metzler, C A Chambers, J P Allison.
Abstract
Similarities in the phenotypes of mice deficient for cytotoxic T lymphocyte antigen-4 (CTLA-4) or transforming growth factor-beta1 (TGF-beta1) 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-beta1(-/-), 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.Entities:
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Year: 2001 PMID： 11226283 PMCID： PMC30182 DOI： 10.1073/pnas.051632398
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205