Cytomegalovirus Reinfections Stimulate CD8 T-Memory Inflation

PLoS One. 2016 Nov 21;11(11):e0167097. doi: 10.1371/journal.pone.0167097. eCollection 2016.

Abstract

Cytomegalovirus (CMV) has been shown to induce large populations of CD8 T-effector memory cells that unlike central memory persist in large quantities following infection, a phenomenon commonly termed "memory inflation". Although murine models to date have shown very large and persistent CMV-specific T-cell expansions following infection, there is considerable variability in CMV-specific T-memory responses in humans. Historically such memory inflation in humans has been assumed a consequence of reactivation events during the life of the host. Because basic information about CMV infection/re-infection and reactivation in immune competent humans is not available, we used a murine model to test how primary infection, reinfection, and reactivation stimuli influence memory inflation. We show that low titer infections induce "partial" memory inflation of both mCMV specific CD8 T-cells and antibody. We show further that reinfection with different strains can boost partial memory inflation. Finally, we show preliminary results suggesting that a single strong reactivation stimulus does not stimulate memory inflation. Altogether, our results suggest that while high titer primary infections can induce memory inflation, reinfections during the life of a host may be more important than previously appreciated.

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Herpesviridae Infections / immunology*
  • Immunologic Memory*
  • Mice
  • Mice, Inbred BALB C
  • Models, Immunological*
  • Muromegalovirus / immunology*

Substances

  • Antibodies, Viral