PMID- 19073721 OWN - NLM STAT- MEDLINE DCOM- 20090216 LR - 20211020 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 83 IP - 5 DP - 2009 Mar TI - Reevaluating the CD8 T-cell response to herpes simplex virus type 1: involvement of CD8 T cells reactive to subdominant epitopes. PG - 2237-45 LID - 10.1128/JVI.01699-08 [doi] AB - 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. FAU - Sheridan, Brian S AU - Sheridan BS AD - Graduate Program in Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. FAU - Cherpes, Thomas L AU - Cherpes TL FAU - Urban, Julie AU - Urban J FAU - Kalinski, Pawel AU - Kalinski P FAU - Hendricks, Robert L AU - Hendricks RL LA - eng GR - T32 AI060525/AI/NIAID NIH HHS/United States GR - T32-AI060525/AI/NIAID NIH HHS/United States GR - R01 EY005945/EY/NEI NIH HHS/United States GR - R01-EY05945/EY/NEI NIH HHS/United States GR - P30-EY08098/EY/NEI NIH HHS/United States GR - P30 EY008098/EY/NEI NIH HHS/United States GR - K23 AI064396/AI/NIAID NIH HHS/United States GR - K23-AI064396/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20081210 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Antigens, Viral) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (Viral Envelope Proteins) RN - 0 (glycoprotein B, Simplexvirus) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Antigens, Viral/immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - Cells, Cultured MH - Epitopes, T-Lymphocyte/*immunology MH - Female MH - Herpes Simplex/*immunology/virology MH - Herpesvirus 1, Human/*immunology/physiology MH - Interferon-gamma/immunology MH - Lymphocyte Activation MH - Mice MH - Mice, Inbred C57BL MH - Trigeminal Ganglion/immunology/virology MH - Viral Envelope Proteins/immunology MH - Virus Latency PMC - PMC2643732 EDAT- 2008/12/17 09:00 MHDA- 2009/02/17 09:00 PMCR- 2009/09/01 CRDT- 2008/12/17 09:00 PHST- 2008/12/17 09:00 [entrez] PHST- 2008/12/17 09:00 [pubmed] PHST- 2009/02/17 09:00 [medline] PHST- 2009/09/01 00:00 [pmc-release] AID - JVI.01699-08 [pii] AID - 1699-08 [pii] AID - 10.1128/JVI.01699-08 [doi] PST - ppublish SO - J Virol. 2009 Mar;83(5):2237-45. doi: 10.1128/JVI.01699-08. Epub 2008 Dec 10.