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Latent Virus Influences the Generation and Maintenance of CD8⁺ T Cell Memory¹

Brian S. Sheridan^*,, Kamal M. Khanna^¶, Gregory M. Frank^*, and Robert L. Hendricks^2,,,

^* Graduate Program in Immunology, Department of Ophthalmology, Department of Molecular Genetics and Biochemistry, and Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; and ^¶ Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030

The influence of latent virus on CD8⁺ T cell memory is poorly understood. HSV type 1 specifically establishes latency in trigeminal ganglia (TG) after corneal infection of mice. In latently infected TG, IL-15 deprivation reduced the following: 1) accumulation of HSV-specific CD8⁺ effector T cells (HSV-CD8_eff), 2) accumulation of CD127⁺ putative HSV-CD8 memory precursors, and 3) the size and functionality of the memory (HSV-CD8_mem) population. Although compromised in IL-15^–/– mice, the HSV-CD8_mem pool persisted in latently infected tissue, but not in noninfected tissue of the same mice. Anti-IL-2 treatment also dramatically reduced the size of the HSV-CD8_eff population in the TG, but did not influence the concomitant generation of the CD127⁺ putative HSV-CD8_mem precursor population or the size or functionality of the HSV-CD8_mem pool. Thus, the size of the memory pool appears to be determined by the size of the CD127⁺ CD8_mem precursor population and not by the size of the overall CD8_eff pool. HSV-CD8_mem showed a higher basal rate of proliferation in latently infected than noninfected tissue, which was associated with a reduced population of CD4⁺FoxP3⁺ regulatory T cells. Thus, the generation, maintenance, and function of memory CD8⁺ T cells is markedly influenced by latent virus.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Support for this work was provided by National Institutes of Health Grants EY05945, P30 EY08098, and T32 AI060525, and an unrestricted grant from Research to Prevent Blindness (New York, NY) and the Eye and Ear Foundation of Pittsburgh.

² Address correspondence and reprint requests to Dr. Robert L. Hendricks, Eye and Ear Institute, Room 922, 203 Lothrop Street, Pittsburgh, PA 15213. E-mail address: hendricksrr{at}upmc.edu

³ Abbreviations used in this paper: LCMV, lymphocytic choriomeningitis virus; TG, trigeminal ganglion; WT, wild type; dpi, days postinfection; HSV-CD8, HSV-1-specific CD8⁺ T cell; Treg, regulatory T cell; DLN, draining lymph node.

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