PD-L1/B7-H1 regulates the survival but not the function of CD8⁺ T cells in herpes simplex virus type 1 latently infected trigeminal ganglia

HSV type 1 (HSV-1)-specific CD8⁺ T cells provide immunosurveillance of trigeminal ganglion (TG) neurons that harbor latent HSV-1. In C57BL/6 mice, the TG-resident CD8⁺ T cells are HSV specific and maintain a 1:1 ratio of cells recognizing an immunodominant epitope on viral glycoprotein B (gB_498-505-Tet⁺) and cells reactive to subdominant epitopes (gB-Tet^-). The gB-Tet^- CD8 ⁺ T cells maintain their frequency in TG by balancing a higher rate of proliferation with a correspondingly higher rate of apoptosis. The increased apoptosis is associated with higher expression of programmed death-1 (PD-1) on gB-Tet^- CD8⁺ T cells and the interaction with PD-1 ligand (PD-L1/B7-H1). IFN-γ regulated expression of the PD-1 ligand (PD-L1/B7-H1) on neurons bearing higher copies of latent viral genome. In latently infected TG of B7-H1^-/- mice, the number and frequency of PD-1⁺ gB-Tet^- CD8⁺ T cells increases dramatically, but gB-Tet^- CD8⁺ T cells remain largely nonfunctional and do not provide increased protection from HSV-1 reactivation in ex vivo cultures of latently infected TG. Unlike observations in some chronic infection models, B7-H1 blockade did not increase the function of exhausted gB-Tet^- CD8 T cells in latently infected TG.