Type 1 Interferon Induction of Natural Killer Cell Gamma Interferon Production for Defense during Lymphocytic Choriomeningitis Virus Infection

Mack, Ethan A.; Kallal, Lara E.; Demers, Delia A.; Biron, Christine A.

The STAT1 and STAT4 levels are differentially expressed in cell subsets during LCMV infection. Because our previous studies have shown that a pathway from type 1 IFN through STAT4 for NK cell IFN-␥ expression in the spleen is associated with high basal STAT4 levels but blocked by increasing STAT1 levels during infections (9), intracellular STAT levels were examined in the peritoneal populations by flow cytometric approaches. The experiments demonstrated high basal STAT4 levels in NK cells (Fig. 5A) . The trait was unique to NK cells, with only low proportions of total lymphocytes and T cells expressing STAT4 and only doing so at lower levels, and NK cells retained their unique high levels of STAT4 throughout infection (Fig. 5A) . In contrast, all populations isolated from uninfected mice were low for STAT1, but expression in the NK cells was always slightly lower (Fig. 5B) . Following LCMV infection, the total lymphocyte and T cell pop-ulations rapidly elevated STAT1 expression, with 80 to 95% of the populations expressing high levels of STAT1 by 40 h after infection ( Fig. 5B to D) . The peritoneal NK cells also had STAT1 levels induced during the infection, but in comparison to the other populations, there was a delay, requiring upwards of 8 to 16 h longer than total lymphocytes and T cells to reach 50% high levels of STAT1-expressing cells (Fig. 5B to E) . Thus, the NK cell populations uniquely express high levels of STAT4 basally and after infection. Moreover, although all populations have elevated STAT1 after infection, induction in NK cells is delayed.