Latent virus influences the generation and maintenance of CD8⁺ T cell memory

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 iniuence 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.