Generation, maintenance and tissue distribution of T cell responses to human cytomegalovirus in lytic and latent infection

Abstract

Understanding how the T cell memory response directed towards human cytomegalovirus (HCMV) develops and changes over time while the virus persists is important. Whilst HCMV primary infection and periodic reactivation is well controlled by T cell responses in healthy people, when the immune system is compromised such as post-transplantation, during pregnancy, or underdeveloped such as in newborn infants and children, CMV disease can be a significant problem. In older people, HCMV infection is associated with increased risk of mortality and despite overt disease rarely being seen there are increases in HCMV-DNA in urine of older people suggesting that there is a change in the efficacy of the T cell response following lifelong infection. Therefore, understanding whether phenomenon such as "memory inflation" of the immune response is occurring in humans and if this is detrimental to the overall health of individuals would enable the development of appropriate treatment strategies for the future. In this review, we present the evidence available from human studies regarding the development and maintenance of memory CD8 + and CD4 + T cell responses to HCMV. We conclude that there is only limited evidence supportive of "memory inflation" occurring in humans and that future studies need to investigate immune cells from a broad range of human tissue sites to fully understand the nature of HCMV T cell memory responses to lytic and latent infection.

Limited effect of duration of CMV infection on adaptive immunity and frailty: insights from a 27‐year‐long longitudinal study

“…23,45,46 Memory inflation of CMV-specific T cells in humans was questioned recently. 47 Longitudinal studies in humans are very limited, and some report evidence for memory inflation, 40,48 while others do not. 49,50 Our study allowed us to investigate how duration of CMV infection influences the T-cell memory pool in humans.…”

Vaccine Vectors Harnessing the Power of Cytomegaloviruses

“…Based on this result from MCMV models, infective augmentation after HCMV immunization could be a possibility. Some of these concerns were alleviated by a cohort study in human volunteers, where no suppressive phenotype was found after lifelong HCMV carriage [176]. Another biosafety issue focuses on the relevance of viral coinfection and its impact on MI, specifically as HIV + CMV + individuals show inflation of CMV epitope-specific CD4 T cells [177].…”

‘Checks and balances’ in cytomegalovirus-host cohabitation

“…I cannot highlight here all the outstanding contributions, but, in editor's view, most challenging for all 'mouse modelers' is the contribution by Jackson and colleagues [4] who conclude "that there is only limited evidence supportive of memory inflation occurring in humans", a conclusion that contradicts the generalized statement found in almost all papers on MI in animal models, namely that "MI is a hallmark of CMV infections". In accordance with missing MI in most human CMV-seropositive but otherwise healthy volunteers, previous protagonists of CMV-associated immunosenescence appear to back away from a relevance in humans [5] and a systematic review and meta-analysis in influenza vaccinees by van den Berg and colleagues [6] arrives at the conclusion "that there is no unequivocal evidence that latent CMV infection affects the influenza antibody response to vaccination".…”