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Review
. 2012 Jul;4(7):1116-43.
doi: 10.3390/v4071116. Epub 2012 Jul 20.

T cell memory in the context of persistent herpes viral infections

Nicole Torti  1 , Annette Oxenius
Affiliations
Review

T cell memory in the context of persistent herpes viral infections

Nicole Torti et al. Viruses. 2012 Jul.

Abstract

The generation of a functional memory T cell pool upon primary encounter with an infectious pathogen is, in combination with humoral immunity, an essential process to confer protective immunity against reencounters with the same pathogen. A prerequisite for the generation and maintenance of long-lived memory T cells is the clearance of antigen after infection, which is fulfilled upon resolution of acute viral infections. Memory T cells play also a fundamental role during persistent viral infections by contributing to relative control and immuosurveillance of active replication or viral reactivation, respectively. However, the dynamics, the phenotype, the mechanisms of maintenance and the functionality of memory T cells which develop upon acute/resolved infection as opposed to chronic/latent infection differ substantially. In this review we summarize current knowledge about memory CD8 T cell responses elicited during α-, β-, and γ-herpes viral infections with major emphasis on the induction, maintenance and function of virus-specific memory CD8 T cells during viral latency and we discuss how the peculiar features of these memory CD8 T cell responses are related to the biology of these persistently infecting viruses.

Keywords: CD8 T cell function; CD8 T cell maintenance; CD8 T cell phenotype; CD8 T cells; herpes virus infection; memory inflation: secondary lymphoid organs; peripheral tissues.

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Figures

Figure 1
Figure 1
(A) CD8 T cell dynamics during acute and latent MCMV infection. The acute phase (“A”) of MCMV infection is characterized by lytic viral replication (pink areas) which is controlled by NK and T cells with an organ-specific kinetics. The following phase of latent infection (“L”) is thought to be associated with local viral reactivation events which are readily controlled by MCMV-specific immunity. CD8 T cell responses specific for the majority of MCMV-derived epitopes follow a classical expansion, contraction and memory phase (green, conventional response) while CD8 T cells with some MCMV-specificities undergo memory inflation (blue, inflationary response), eventually stabilizing at high numbers with an activated phenotype. (B) CD8 T cell priming in secondary lymphoid organs. Priming of conventional and inflationary MCMV-specific CD8 T cell responses occurs in secondary lymphoid organs and largely depends on the presence of cross-presentation competent dendritic cells. Activated MCMV-specific CD8 T cells, equipped with effector functions, exit secondary lymphoid organs and home to peripheral tissues where they contribute to control of lytic MCMV replication; (C) Memory CD8 T cell inflation during latent MCMV infection. Inflationary MCMV-specific CD8 T cells accumulate in peripheral tissues where they are maintained at high numbers with an effector memory phenotype. This memory CD8 T cell inflation is triggered by MCMV antigen recognition on latently infected non-hematopoietic cells within lymph nodes where inflationary CD8 T cells exhibiting a central memory phenotype are restimulated to proliferate, to acquire effector phenotypes and to migrate into peripheral tissues where they contribute to local immune-surveillance of latent/reactivating MCMV infection.
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