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Journal of Virology, March 2009, p. 2237-2245, Vol. 83, No. 5
0022-538X/09/$08.00+0     doi:10.1128/JVI.01699-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Reevaluating the CD8 T-Cell Response to Herpes Simplex Virus Type 1: Involvement of CD8 T Cells Reactive to Subdominant Epitopes{triangledown}

Brian S. Sheridan,1,2,{dagger} Thomas L. Cherpes,1,3 Julie Urban,4 Pawel Kalinski,4 and Robert L. Hendricks2,5,6*

Graduate Program in Immunology,1 Departments of Ophthalmology,2 Obstetrics, Gynecology, and Reproductive Sciences,3 Surgery,4 Molecular Genetics and Biochemistry,5 Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania6

Received 9 August 2008/ Accepted 3 December 2008

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.

* Corresponding author. Mailing address: Eye and Ear Institute, Rm. 922, 203 Lothrop St., Pittsburgh, PA 15213. Phone: (412) 647-5754. Fax: (412) 647-5880. E-mail: hendricksrr{at}upmc.edu

{triangledown} Published ahead of print on 10 December 2008.

{dagger} Present address: Department of Immunology, University of Connecticut Health Center, Farmington, CT.

Journal of Virology, March 2009, p. 2237-2245, Vol. 83, No. 5
0022-538X/09/$08.00+0     doi:10.1128/JVI.01699-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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