Effector function and efficacy of CD8+ T cells activated in the absence of IFN‐γ

Abstract

We examined the influence of early IFN‐γ exposure on CD8+ T cell effector function. Immunization of C57BL/6 mice with a thymidine kinase deficient herpes simplex virus type 2 (HSV‐2 TK‐) elicited CD8+ T cells secreting mainly IFN‐γ and TNF‐α (Tc1), whereas CD8+ T cells from immunized IFN‐γ−/−mice secreted mainly TNF‐α with a lesser population secreting type 2 cytokines (Tc2). To facilitate studies of the effector function of these cells we cultured OT‐I CD8+ T cells in conditions that generated Tc1 or Tc2. Like CD8+ T cells from IFN‐γ−/−mice, Tc2 secreted type 2 cytokines, IL‐4, IL‐5 and IL‐10 with a distinct population producing IFN‐γ and TNF‐α. Tc1 produced both IFN‐γ and TNF‐α, like B6 CD8+ T cells. Tc1 and Tc2 expressed similar surface activation and differentiation markers. Tc2 exhibited delayed proliferation and reduced CTL activity in vivo, when compared to Tc1. These differences correlated with a delay in clearance of an OVA expressing HSV‐2 strain by Tc2 recipients, relative to Tc1 recipients. Despite the ability to secrete regulatory cytokines, such as IL‐10, co‐transfer of Tc2 with Tc1 did not interfere with the Tc1‐mediated virus clearance. Together these results suggest that early exposure to IFN‐γnot only imprints type 1 cytokine secretion, but also affects proliferation and cytolysis. Supported by NIH AI42815 and AI054444. MHN supported by a Sealy Center for Vaccine Development Predoctoral Fellowship.