Respiratory Syncytial Virus–Specific CD8<sup>+</sup>Memory T Cell Responses in Elderly Persons

Bree, Godelieve J. de; Heidema, Jojanneke; Leeuwen, Ester M. M. van; Bleek, Grada M. van; Jonkers, René E.; Jansen, Henk M.; Lier, R. A. W. Van; Out, Theo A.

doi:10.1086/429695

Cited by 101 publications

(90 citation statements)

References 29 publications

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“…Newborn CBMCs are naïve and devoid of RSV‐specific memory T cells whereas adults contain RSV‐specific memory T cells 17. Significant amounts of IFN‐γ were measured in the supernatant of adult MCs two days after exposure to RSV, whereas IFN‐γ was not detectable in supernatants from newborn MCs (Fig.…”

Section: Resultsmentioning

confidence: 93%

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

et al. 2018

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Interferon gamma (IFN‐γ) plays an important role in the antiviral immune response during respiratory syncytial virus (RSV) infections. Monocytes and T cells are recruited to the site of RSV infection, but it is unclear whether cell‐cell interactions between monocytes and T cells regulate IFN‐γ production. In this study, micro‐array data identified the upregulation of sialic acid‐binding immunoglobulin‐type lectin 1 (Siglec‐1) in human RSV‐infected infants. In vitro, RSV increased expression of Siglec‐1 on healthy newborn and adult monocytes. RSV‐induced Siglec‐1 on monocytes inhibited IFN‐γ production by adult CD4+ T cells. In contrast, IFN‐γ production by RSV in newborns was not affected by Siglec‐1. The ligand for Siglec‐1, CD43, is highly expressed on adult CD4+ T cells compared to newborns. Our data show that Siglec‐1 reduces IFN‐γ release by adult T cells possibly by binding to the highly expressed CD43. The Siglec‐1‐dependent inhibition of IFN‐γ in adults and the low expression of CD43 on newborn T cells provides a better understanding of the immune response against RSV in early life and adulthood.

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Section: Resultsmentioning

confidence: 93%

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

et al. 2018

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“…Besides antibodies, T cells are important for an effective immune response required to clear virus. Since functionality and numbers of RSV-specific CD4 ϩ and CD8 ϩ T cells drop with age (28,44,45), it would be useful to unravel how T-cell responses at old age are involved in the induction of protective immunity by RSV vaccines and how these responses can be improved to act in concert with antibodies to achieve protection at old age.…”

Section: Fig 3 Rhrsv Vaccine-induced Serum Igg Cotton Rats At the Agmentioning

confidence: 99%

Impaired Immune Response to Vaccination against Infection with Human Respiratory Syncytial Virus at Advanced Age

Guichelaar

Hoeboer

Widjojoatmodjo

et al. 2014

J Virol

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Elderly humans are prone to severe infection with human respiratory syncytial virus (HRSV). The aging of today's human population warrants the development of protective vaccination strategies aimed specifically at the elderly. This may require special approaches due to deteriorating immune function. To design and test vaccination strategies tailored to the elderly population, we need to understand the host response to HRSV vaccination and infection at old age. Moreover, the preclinical need for testing of candidate vaccines requires translational models resembling susceptibility to the (unadapted) human pathogen. Here, we explored the effects of aging on immunity and protection induced by a model HRSV vaccine candidate in a translational aging model in cotton rats (Sigmodon hispidus) and examined possibilities to optimize vaccination concepts for the elderly. We immunized young and aged cotton rats with a live-attenuated recombinant HRSV vaccine candidate and analyzed the induced immune response to and protection against challenge with HRSV. In old cotton rats, HRSV infection persisted longer, and vaccination induced less protection against infection. Aged animals developed lower levels of vaccine-induced IgG, virus-neutralizing serum antibodies, and IgA in lungs. Moreover, booster responses to HRSV challenge were impaired in animals vaccinated at an older age. However, increased dose and reduced attenuation of vaccine improved protection even in old animals. This study shows that cotton rats provide a model for studying the effects of aging on the immune response to the human respiratory pathogen HRSV and possibilities to optimize vaccine concepts for the elderly. IMPORTANCEHRSV infection poses a risk for severe disease in the elderly. The aging of the population warrants increased efforts to prevent disease at old age, whereas HRSV vaccines are only in the developmental phase. The preclinical need for testing of candidate human vaccines requires translational models resembling susceptibility to the natural human virus. Moreover, we need to gain insight into waning immunity at old age, as this is a special concern in vaccine development. In this study, we explored the effect of age on protection and immunity against an experimental HRSV vaccine in aged cotton rats (Sigmodon hispidus), a rodent species that provides a model representing natural susceptibility to human viruses. Older animals generate fewer antibodies upon vaccination and require a higher vaccine dose for protection. Notably, during the early secondary immune response to subsequent HRSV infection, older animals showed less protection and a slower increase of the virus-neutralizing antibody titer.

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“…This process of effector cell recruitment is enhanced during infections when local chemokine production is up-regulated. When infections are cleared, substantial numbers of T cells remain detectable in the lung tissue and airways (5,6). The role of different T cell populations that are recruited into lung tissue and the airways in the process of viral eradication is still unclear, as is the mechanism by which the balance between the different T cell populations is reinstilled in peripheral blood after viral clearance.…”

Section: A Ntiviral Cd8mentioning

confidence: 99%

“…To investigate the disappearance of virus-specific CD8 ϩ T cells during infections with heterologous viruses without the need of in vitro expansion, we also determined the influenza virus-specific T cell numbers that are present in higher frequencies in peripheral blood (5). In these experiments we performed direct staining in four HLA-A2-positive donors with HLA-A2 tetrameric complexes containing peptide M1 58 -66 derived from the influenza matrix protein.…”

Section: During Respiratory Viral Infections Bystander Cd8 ϩ T Cellsmentioning

confidence: 99%

Dynamics of Human Respiratory Virus-Specific CD8+ T Cell Responses in Blood and Airways during Episodes of Common Cold

Heidema

Rossen²,

Lukens

et al. 2008

The Journal of Immunology

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We determined the dynamics of CD8+ T cells specific for influenza virus and respiratory syncytial virus in blood and tracheostoma aspirates of children during the course of respiratory infections. We showed that during localized respiratory infections the ratio of activated effector CD8+ T cells to resting memory/naive CD8+ T cells in peripheral blood increased significantly. Furthermore, the number of effector/memory T cells specific for respiratory viruses declined in blood and increased in the airways, suggesting that these T cells redistributed from blood to airways. T cells specific for the infecting virus were present in the airways for longer periods at increased levels than nonspecifically recruited bystander T cells. After clearance of the infection, the ratio of resting memory and naive CD8+ T cells normalized in peripheral blood and also memory T cell numbers specific for unrelated viruses that declined during the infection due to bystander recruitment were restored. Taken together, these results showed a significant systemic T cell response during relatively mild secondary infections and extensive dynamics of virus-specific and nonspecific Ag-experienced T cells.

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Respiratory Syncytial Virus–Specific CD8⁺Memory T Cell Responses in Elderly Persons

Cited by 101 publications

References 29 publications

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

Impaired Immune Response to Vaccination against Infection with Human Respiratory Syncytial Virus at Advanced Age

Dynamics of Human Respiratory Virus-Specific CD8+ T Cell Responses in Blood and Airways during Episodes of Common Cold

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Respiratory Syncytial Virus–Specific CD8+Memory T Cell Responses in Elderly Persons

Cited by 101 publications

References 29 publications

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

Impaired Immune Response to Vaccination against Infection with Human Respiratory Syncytial Virus at Advanced Age

Dynamics of Human Respiratory Virus-Specific CD8+ T Cell Responses in Blood and Airways during Episodes of Common Cold

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Respiratory Syncytial Virus–Specific CD8⁺Memory T Cell Responses in Elderly Persons