期刊
NATURE IMMUNOLOGY
卷 2, 期 12, 页码 1174-1182出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni730
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- NHLBI NIH HHS [HL 54786] Funding Source: Medline
- NIAID NIH HHS [AI 41584, AI 43552] Funding Source: Medline
During a search for genes that maintain T cell quiescence, we determined that Tob, a member of an anti-proliferative gene family, was highly expressed in anergic T cell clones. Tob was also expressed in unstimulated peripheral blood T lymphocytes and down-regulated during activation. Forced expression of Tob inhibited T cell proliferation and transcription of cytokines and cyclins. In contrast, suppression of Tob with an antisense oligonucleotide augmented CD3-mediated responses and abrogated the requirement of costimulation for maximal proliferation and cytokine secretion. Tob associated with Smad2 and Smad4 and enhanced Smad DNA-binding. The inhibitory effect of Tob on interleukin 2 (IL-2) transcription was not mediated by blockade of NFAT, AP-1 or NF-kappaB transactivation but by enhancement of Smad binding on the -105 negative regulatory element of the IL-2 promoter. Thus,T cell quiescence is an actively maintained phenotype that must be suppressed for T cell activation to occur.
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