title: Reevaluating the CD8 T-cell response to herpes simplex virus type 1: involvement of CD8 T cells reactive to subdominant epitopes.
abstract: In C57BL/6 (B6) mice, most herpes simplex virus (HSV)-specific CD8 T cells recognize a strongly immunodominant epitope on glycoprotein B (gB498) and can inhibit HSV type 1 (HSV-1) reactivation from latency in trigeminal ganglia (TG). However, half of the CD8 T cells retained in latently infected TG of B6 mice are not gB498 specific and have been largely ignored. The following observations from our current study indicate that these gB498-nonspecific CD8 T cells are HSV specific and may contribute to the control of HSV-1 latency. First, following corneal infection, OVA257-specific OT-1 CD8 T cells do not infiltrate the infected TG unless mice are simultaneously immunized with OVA257 peptide, and then they are not retained. Second, 30% of CD8 T cells in acutely infected TG that produce gamma interferon in response to HSV-1 stimulation directly ex vivo are gB498 nonspecific, and these cells maintain an activation phenotype during viral latency. Finally, gB498-nonspecific CD8 T cells are expanded in ex vivo cultures of latently infected TG and inhibit HSV-1 reactivation from latency in the absence of gB498-specific CD8 T cells. We conclude that many of the CD8 T cells that infiltrate and are retained in infected TG are HSV specific and potentially contribute to maintenance of HSV-1 latency. Identification of the viral proteins recognized by these cells will contribute to a better understanding of the dynamics of HSV-1 latency.
authors.affiliation: Graduate Program in Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Sheridan
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Cherpes
authors.forename: Julie
authors.initials: J
authors.lastname: Urban
authors.forename: Pawel
authors.initials: P
authors.lastname: Kalinski
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hendricks
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000502:physiology; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D012668:Trigeminal Ganglion / Q000276:immunology / Q000821:virology; D014759:Viral Envelope Proteins / Q000276:immunology; D017735:Virus Latency
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; D007371:Interferon-gamma