HSV induces an early primary Th1 CD4 T cell response in neonatal mice, but reduced CTL activity at the time of the peak adult response

Neonates are highly susceptible to HSV. In this study, we analyzed the primary neonatal cell‐mediated response to HSV at the site of T cell activation, the draining lymph nodes (LN), and examined the effects of dose and the ability of HSV to replicate on the strength and character of this response. Neonatal mice mounted a predominantly Th1 cytokine (IFN‐γ) response at all doses of a replication‐competent thymidine kinase‐negative HSV‐2 strain (186ΔKpn) and at high doses of a replication‐defective HSV‐2 virus (dl5–29, UL5–/UL29–). Both neonates and adults showed increased production of Th2 cytokines (IL‐4 and/or IL‐5) at high doses of the replication‐defective or inactivated HSV strains. An age‐dependent difference in the strength of the Th1 response was noted, with neonates mounting adult‐like responses at low but not high doses of HSV. Neonatal mice also showed impaired CD8+ T cell activation and reduced HSV‐specific CTL effector function at the time of the peak adult response. These studies are the first to highlight the impaired primary neonatal T cell response to HSV in the LN.