title: 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.
abstract: 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 (gB498-505-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.
authors: Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors: Sohyun
authors: S
authors: Jeon
authors: Anthony J
authors: AJ
authors: St Leger
authors: Thomas L
authors: TL
authors: Cherpes
authors: Brian S
authors: BS
authors: Sheridan
authors: Robert L
authors: RL
authors: Hendricks
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D060890:B7-H1 Antigen / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D012668:Trigeminal Ganglion / Q000821:virology; D017735:Virus Latency / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse
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