Contemporaneous fluctuations in T cell responses to persistent herpes virus infections

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Abstract
The classical paradigm for T cell dynamics suggests that the resolution of a primary acute virus infection is followed by the generation of a long‐lived pool of memory T cells that is thought to be highly stable. Very limited alteration in this repertoire is expected until the immune system is re‐challenged by reactivation of latent viruses or by cross‐reactive pathogens. Contradicting this view, we show here that the T cell repertoire specific for two different latent herpes viruses in the peripheral blood displayed significant contemporaneous co‐fluctuations of virus‐specific CD8+ T cells. The coordinated responses to two different viruses suggest that the fluctuations within the T cell repertoire may be driven by sub‐clinical viral reactivation or a more generalized ‘bystander’ effect. The later contention was supported by the observation that, while absolute number of CD3+ T cells and their subsets and also the cell surface phenotype of antigen‐specific T cells remained relatively constant, a loss of CD62L expression in the total CD8+ T cell population was coincident with the expansion of tetramer‐positive virus‐specific T cells. This study demonstrates that the dynamic process of T cell expansion and contractions in persistent viral infections is not limited to the acute phase of infection, but also continues during the latent phase of infection.