Differential transcription of Eomes and T-bet during maturation of mouse uterine natural killer cells

Abstract: During human and rodent uterine de-cidualization, transient but abundant numbers of uterine natural killer (uNK) cells appear, prolifer-ate, and differentiate. uNK cells share features with peripheral NK cells but are specialized to promote interferon- (IFN-)-mediated, preg-nancy-associated, structural changes in maternal placental arteries. In CD8 T cells and NK cells, the transcription factors T-bet and eomesodermin (Eomes) regulate maturation and effector func-tions, including IFN- production. No studies are reported for uNK cells. Implantation sites in T-bet null mice, which have a defect in NK cell matura-tion, had uNK cells normal in morphology and number and normally modified spiral arteries. As Eomes null mice are not viable, real-time polymer-ase chain reaction comparisons between C57Bl/6J (B6) and alymphoid (Rag20/0c0/0) mice were used to assess uNK cell expression of T-bet, Eomes, and the target genes IFN-, granzyme A, and perforin. Gestation dated (gd) uterine tissues (mixed cell composition) and 200 morphologically homoge-neous, laser-capture, microdissected uNK cells of different maturation stages were used. In uterus, Eomes transcripts greatly outnumbered those of T-bet, whether donors were nonpregnant or preg-nant, and increased to gd10. In uNK cells, tran-scripts for T-bet, Eomes, and IFN- were most abundant in mature stage cells, and transcripts for granzyme A and perforin were lower at this stage than in immature or senescent cells. Thus, Eomes dominance to T-bet discriminates regulation of the uNK cell subset from that observed for peripheral NK cells. J. Leukoc. Biol. 78: 000–000; 2005. Key Words: cell differentiation granzyme interferon- perforin reproductive immunology transcription factor