Journal
NATURE IMMUNOLOGY
Volume 3, Issue 7, Pages 652-658Publisher
NATURE AMERICA INC
DOI: 10.1038/ni807
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- NIAID NIH HHS [AI42370] Funding Source: Medline
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Type 1 helper T (T(H)1) cells are essential for cellular immunity, but their ontogeny, maturation and durability remain poorly understood. By constructing a dominant-negative form of T-bet, we were able to determine the role played by this lineage-inducing trans-activator in the establishment and maintenance of heritable T(H)1 gene expression. Optimal induction of interferon-gamma (IFN-gamma) expression required genetic interaction between T-bet and its target, the homeoprotein Hlx. In fully mature T(H)1 cells, reiteration of IFN-gamma expression and stable chromatin remodeling became relatively independent of T-bet activity and coincided with demethylation of DNA. In contrast, some lineage attributes, such as expression of IL-12Rbeta2 (interleukin 12 receptor beta2), required ongoing T-bet activity in mature THI cells and their progeny. These findings suggest that heritable states of gene expression might be maintained by continued expression of the inducing factor or by a mechanism that confers a stable imprint of the induced state.
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