Development of CD8 T-memory inflation after cytomegalovirus infection determined by initial viral burden (39.28)

Abstract

Abstract Both mice and humans can develop large “inflated” populations of CD8 effector memory T-cells after cytomegalovirus (CMV) infection, and such memory inflation has been associated with immune senescence. Not all humans develop CD8 memory inflation after CMV infection, so we hypothesized that memory inflation might be predicated by the initial viral burden. Because it is impossible to know an individuals CMV inoculum during natural infection, we infected mice with murine CMV (MCMV) titers ranging from 102 to 106 PFU. After infection, peripheral blood was evaluated monthly for MCMV-specific CD8 T-cells and antibody. Using MCMV-specific MHC class I tetramers we confirm that high titer infections induce inflationary T-memory responses. In contrast, low titer infections induce significantly less inflation over time. Serum ELISA for MCMV-antibody responses showed a similar pattern. DNA from lung tissues evaluated 16 weeks after infection confirmed successful infection in all mice. Quantitative PCR showed that latent viral load in lungs correlated well with eventual lung resident T-memory responses (R2=0.96). We therefore conclude that an individual’s initial infectious burden determines their latent viral load and eventual development of memory inflation after cytomegalovirus infection, possibly explaining the wide variability in T-cell responses to CMV observed in humans.