Viral inoculum dose impacts memory <scp>T</scp>‐cell inflation

Redeker, Anke; Welten, Suzanne P. M.; Arens, Ramon

doi:10.1002/eji.201343946

Cited by 73 publications

(103 citation statements)

References 53 publications

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“…The cell phenotype is once again tightly maintained. Data with similar implications are obtained by experiments in the MCMV model, where the populations expanded by low‐dose infection can be further boosted (and driven toward a more differentiated phenotype) in response to reinfections 49, 68, 69…”

Section: What Is Memory Inflation Now?supporting

confidence: 60%

The (gradual) rise of memory inflation

Klenerman

2018

Immunological Reviews

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SummaryMemory inflation, as a term, has been used for 15 years now to describe the longitudinal development of stable, expanded CD8+ T memory pools with a distinct phenotype and functional profile which emerge in specific infection and vaccine settings. These settings have in common the persistence of antigen, especially cytomegalovirus infection but also more recently adenoviral vector vaccination. However, in contrast to chronic infections which lead to “exhaustion” the repeated antigen encounters experienced by CD8+ T cells lead to development of a robust T‐cell population structure which maintains functionality and size. In this review, I will discuss how the ideas around this form of memory have evolved over time and some new models which can help explain how these populations are induced and sustained. These models are relevant to immunity against persistent viruses, to novel vaccine strategies and to concepts about aging.

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Section: What Is Memory Inflation Now?supporting

confidence: 60%

The (gradual) rise of memory inflation

Klenerman

2018

Immunological Reviews

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“…Recently, it was shown that a low-dose inoculum of MCMV results in a severely hampered inflation of memory T-cells (Redeker et al, 2014), suggesting that the amount of virus is also a determinant of memory inflation. While it is generally accepted that systemic infection occurs during congenital HCMV infection by transfer of the virus through the placenta, infections after birth most likely occur via mucosal routes.…”

Section: Discussionmentioning

confidence: 99%

“…5), our data imply that latent viral load in the spleen, rather than in the lungs, predicts the magnitude of memory inflation, consistent with the recent observation that CMV-specific T-cells proliferate in the spleen of latently infected mice upon i.p. infection (Redeker et al, 2014). We focused in our study on prototypical inflationary epitopes.…”

Section: Discussionmentioning

confidence: 99%

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Murine cytomegalovirus (CMV) infection via the intranasal route offers a robust model of immunity upon mucosal CMV infection

Oduro

Redeker

Lemmermann

et al. 2016

Journal of General Virology

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Cytomegalovirus (CMV) is a ubiquitous virus, causing the most common congenital infection in humans, yet a vaccine against this virus is not available. Experimental studies of immunity against CMV in animal models of infection, such as the infection of mice with mouse CMV (MCMV), have relied mainly on parenteral infection protocols, although the virus naturally transmits by mucosal routes via body fluids. To characterize the biology of infections by mucosal routes, we compared the kinetics of virus replication, latent viral load and CD8 T-cell responses in lymphoid organs upon experimental intranasal (targeting the respiratory tract) and intragastric (targeting the digestive tract) infection with systemic intraperitoneal infection of two unrelated mouse strains. We observed that intranasal infection induced robust and long-term virus replication in the lungs and salivary glands but limited replication in the spleen. CD8 T-cell responses were somewhat weaker than upon intraperitoneal infection but showed similar kinetic profiles and phenotypes of antigen-specific cells. In contrast, intragastric infection resulted in abortive or poor virus replication in all tested organs and poor T-cell responses to the virus, especially at late times after infection. Consistent with the T-cell kinetics, the MCMV latent load was high in the lungs but low in the spleen of intranasally infected mice and lowest in all tested organs upon intragastric infection. In conclusion, we showed that intranasal but not intragastric infection of mice with MCMV represents a robust model to study the short-and long-term biology of CMV infection by a mucosal route.

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“…In mice, it has been shown that viral inoculum dose impacts the degree of CMV-specific memory T cell inflation and the phenotype of memory subsets (Redeker et al 2014). Of note, the studies to date that explore the relationship between immunosenescence and the size of the CMV-specific T cell response in humans have considered mainly interferon-γ (IFN-γ) secretion in response to a restricted number of target proteins, especially UL83 or UL123.…”

Section: T Cell Phenotypesmentioning

confidence: 99%

A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness

Souquette¹,

Frere²,

Smithey³

et al. 2017

GeroScience

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Approximately 50% of individuals aged 6-49 years in the United States are infected with cytomegalovirus (CMV), with seroprevalence increasing with age, reaching 85-90% by 75-80 years according to Bate et al. (Clin Infect Dis 50 (11): 1439-1447 and Pawelec et al. (Curr Opin Immunol 24:507-511, 2012). Following primary infection, CMV establishes lifelong latency with periodic reactivation. Immunocompetent hosts experience largely asymptomatic infection, but CMV can cause serious illness in immunocompromised populations, such as transplant patients and the elderly. Control of CMV requires constant immune surveillance, and recent discoveries suggest this demand alters general features of the immune system in infected individuals. Here, we review recent advances in the understanding of the immune response to CMV and the role of CMV in immune aging and fitness, while highlighting the importance of potential confounding factors that influence CMV studies. Understanding how CMV contributes to shaping Bbaseline^immunity has important implications for a host's ability to mount effective responses to diverse infections and vaccination.

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Viral inoculum dose impacts memory T‐cell inflation

Cited by 73 publications

References 53 publications

The (gradual) rise of memory inflation

The (gradual) rise of memory inflation

Murine cytomegalovirus (CMV) infection via the intranasal route offers a robust model of immunity upon mucosal CMV infection

A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness

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