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

Abstract

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-CD8eff), 2) accumulation of CD127+ putative HSV-CD8 memory precursors, and 3) the size and functionality of the memory (HSV-CD8mem) population. Although compromised in IL-15−/− mice, the HSV-CD8mem 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-CD8eff population in the TG, but did not influence the concomitant generation of the CD127+ putative HSV-CD8mem precursor population or the size or functionality of the HSV-CD8mem pool. Thus, the size of the memory pool appears to be determined by the size of the CD127+ CD8mem precursor population and not by the size of the overall CD8eff pool. HSV-CD8mem 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.