Distinct stage-specific function of T-box transcription factors in the antiviral NK cell response (IRM14P.446)

Abstract The T-box transcription factors T-bet and Eomesodermin (Eomes) instruct discrete stages of natural killer (NK) cell development. Their role in the response of mature NK cells against pathogen infection has not been investigated. Here, we use an inducible gene deletion system to elucidate the role of T-bet and Eomes in mature NK cells during the course of murine cytomegalovirus (MCMV) infection. We show that although both transcription factors are dispensable for maintaining NK cell numbers during homeostatic proliferation, T-bet and Eomes are necessary for the proliferation of virus-specific NK cells during MCMV infection. T-bet, but not Eomes, is upregulated in NK cells early after viral infection, through pro-inflammatory cytokine and STAT4 signaling. However, deletion of either T-bet or Eomes in mature NK cells during viral infection led to a diminished NK cell response in lymphoid and nonlymphoid organs. Interestingly, maintenance of memory NK cell numbers was dependent on T-bet, but not Eomes. These data uncover a non-redundant and stage-specific influence of T-bet and Eomes on the NK cell response against infection.