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.
Highlights
Generation of immunological memory after infection is a cornerstone of immunity, providing hosts with long-term protection against infectious diseases and providing the basis for all vaccines
Recent work has suggested that lower doses of murine CMV (mCMV) during primary infection influence the absolute magnitude of the CD8 T-cell response [24, 27], but not the early expansion/ contraction of mCMV-specific T-cells nor early development of T-memory [15]
We evaluated mCMV specific T-cell responses after infections with 102−106 pfu Smith mCMV
Summary
Generation of immunological memory after infection is a cornerstone of immunity, providing hosts with long-term protection against infectious diseases and providing the basis for all vaccines. Many pathogens induce prompt T-cell responses that initially expand in response to infections, contract to a small population of persistent central-memory cells. Induce large T-cell responses that persist and do not contract, a phenomenon described as “memory inflation”. Such T-memory inflation has been described for several pathogens, including members of the herpes virus family (herpes simplex viruses and cytomegaloviruses), murine polyoma virus, and acute parvovirus B19 [1,2,3,4]. The best studied are the cytomegaloviruses (CMV), ubiquitous pathogens classified within the Beta herpesvirinae subfamily.
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