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.

To determine the role of STAT4 in NK cell IFN-␥ expression, responses in mice lacking STAT4 as a result of genetic mutation (STAT4 Ϫ/Ϫ ) (13) were evaluated. Here, the PECs were isolated from uninfected mice and mice at 30 or 36 h after LCMV infections (Fig. 4A ). NK cells from infected STAT4-deficient mice were induced to express much lower levels of IFN-␥ and did so in lower frequencies than NK cells from infected WT mice (Fig. 4A ). To define the effects of STAT4 loss within NK cells in a WT environment of infection, adoptive transfer experiments were carried out using PEC donor cells isolated from WT or STAT4-deficient mice and then delivered into WT recipient mice. The donor cells were identified by lack of CD45.1 expression and the recipient cells by CD45. IFN-␥ at 30 h after infection. In contrast, when STAT4 Ϫ/Ϫ cells were transferred, donor NK cells produced significantly lower levels of IFN-␥ compared to WT recipient NK cells in response to infection (Fig. 4B) . Hence, STAT4 expression within peritoneal NK cells is necessary for optimal IFN-␥ induction.