Abstract
Memory T cell inflation is a process in which a subset of cytomegalovirus (CMV) specific CD8 T cells continuously expands mainly during latent infection and establishes a large and stable population of effector memory cells in peripheral tissues. Here we set out to identify in vivo parameters that promote and limit CD8 T cell inflation in the context of MCMV infection. We found that the inflationary T cell pool comprised mainly high avidity CD8 T cells, outcompeting lower avidity CD8 T cells. Furthermore, the size of the inflationary T cell pool was not restricted by the availability of specific tissue niches, but it was directly related to the number of virus-specific CD8 T cells that were activated during priming. In particular, the amount of early-primed KLRG1- cells and the number of inflationary cells with a central memory phenotype were a critical determinant for the overall magnitude of the inflationary T cell pool. Inflationary memory CD8 T cells provided protection from a Vaccinia virus challenge and this protection directly correlated with the size of the inflationary memory T cell pool in peripheral tissues. These results highlight the remarkable protective potential of inflationary CD8 T cells that can be harnessed for CMV-based T cell vaccine approaches.
Highlights
A hallmark of immunological memory is the ability of the adaptive immune system to generate long-lived antigen-specific memory T or B cells
Tcell receptors (TCR) exhibit different avidity to a certain MHCI-antigen complex, and usually T cells recognising their cognate antigen with high avidity will be activated and contribute strongly to an effective cytotoxic CD8 T cell response
As low avidity CD8 T cells were reported to contribute to memory inflation during HCMV infection [28], we addressed the question whether TCR avidity plays a role for memory inflation in murine cytomegalovirus (MCMV) infection
Summary
A hallmark of immunological memory is the ability of the adaptive immune system to generate long-lived antigen-specific memory T or B cells. Sporadic viral reactivation events can occur in response to various external stimuli [5, 6], leading to reactivation of the lytic program and to expression of viral proteins whose peptides will be presented to CD8 T cells. This leads to sporadic reactivation and stimulation of memory CD8 T cells with specificity for those antigens, resulting in a pool of functional effector-like and not exhausted CD8 T cells [7,8,9,10]
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