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Divergent Requirement of T-Box Transcription Factors in Effector and Memory NK Cells.

Research paper by Sharline S Madera, Clair D CD Geary, Colleen M CM Lau, Olga O Pikovskaya, Steven L SL Reiner, Joseph C JC Sun

Indexed on: 15 Feb '18Published on: 15 Feb '18Published in: Journal of immunology (Baltimore, Md. : 1950)



Abstract

The T-box transcription factors T-bet and Eomesodermin (Eomes) instruct discrete stages in NK cell development. However, their role in the immune response of mature NK cells against pathogens remains unexplored. We used an inducible deletion system to elucidate the cell-intrinsic role of T-bet and Eomes in mature NK cells during the course of mouse CMV infection. We show both T-bet and Eomes to be necessary for the expansion of virus-specific NK cells, with T-bet upregulation induced by IL-12 signaling and STAT4 binding to a conserved enhancer region upstream of theloci. Interestingly, our data suggest maintenance of virus-specific memory NK cell numbers and phenotype was dependent on T-bet, but not Eomes. These findings uncover a nonredundant and stage-specific influence of T-box transcription factors in the antiviral NK cell response.