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Science  18 Nov 2005:
Vol. 310, Issue 5751, pp. 1091
DOI: 10.1126/science.310.5751.1091b

The transcription factor T-bet, encoded by Tbx21, is a critical regulator of T helper cell type 1 differentiation. Nevertheless, in the development of CD8 functions such as cytotoxicity and interferon-γ production, T-bet function appears to overlap with that of a related transcription factor, eomesodermin (Eomes).

Intlekofer et al. explored this relationship by engineering combined genetic deficiencies of the two transcription factors. Because deletion of both Eomes alleles results in embryonic lethality, mice carrying heterozygous Eomes mutations were crossed with those carrying Tbx21 mutations. Even with only a partial loss of Eomes, this led to significant diminution in both the number and function of memory CD8+ T cells and natural killer cells, which resembles the phenotype of mice lacking the cytokine interleukin (IL)-15. Furthermore, this correlated with the loss of a marker for IL-15 responsiveness, suggesting a direct coupling of Eomes/T-bet activity with the acquisition of IL-15-directed cellular immune functions, including the long-term renewal of CD8+ memory T cells. — SJS

Nat. Immunol. 10.1038/ni1268 (2005).

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