Activation of naïve CD8 T cells requires several signals including TCR ligation and costimulation. Although these signals induce division, accumulation of activated CD8 T cells is dependent on a third signal provided by inflammatory cytokines. In vitro studies suggest that “signal 3”specifically enhances survival; however, the mechanisms for optimal accumulation of activated CD8 T cells in vivo is unknown. To explore these mechanisms, we transfer ~600 OT-I tg-CD8 T cells into congenic hosts and immunize hosts with OVA257-coated dendritic cells in the absence (DC) or presence of inflammation (CpG; DC+CpG). OT-I numbers were similar in DC and DC+CpG recipients at day 5 p.i. However, the presence of inflammation during immunization increased accumulation and extended division of OT-I at day 6-7 p.i. while not altering survival. Extended division of DC+CpG OT-I depended on the maintenance of IL-2/PI3K signaling that was regulated by early/direct IL-12 signaling. These findings indicate that "signal 3" enhances accumulation by maintaining division (not survival) of activated CD8 T cells in a manner dependent on a temporally orchestrated sequence of cytokine signals.
- Copyright © 2013 by The American Association of Immunologists, Inc.