Neonatal influenza-specific effector CTLs retain elevated CD31 levels at the site of infection and have decreased IFN-γ production

Fike, Adam J; Kumova, Ogan K.; Tardif, Virginie; Carey, Alison J.

doi:10.1002/jlb.4a0518-191r

Cited by 5 publications

(9 citation statements)

References 48 publications

(120 reference statements)

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“…During acute respiratory viral infection, 3‐day old murine neonates have an increased frequency of activated viral specific CD31 + CD8 + T cells within the lung at the peak of the lymphocyte response compared to 7‐day old neonates and adults . CD31 + neonatal viral‐specific CTLs exhibit reduced IFNγ production and proliferation .…”

Section: Tcr Inhibitory Moleculesmentioning

confidence: 99%

“…CD31 + neonatal viral‐specific CTLs exhibit reduced IFNγ production and proliferation . CD31 transcript levels are dramatically elevated in sorted CD31 + effector CTLs from neonatally infected mice, which indicate a preferential continued expression in neonatal CTLs, compared to naïve or adult effector T‐cell populations . In support of a differential regulation of CD31 expression between neonates and adult mice, CD8 + T cells expressing a transgenic TCR specific for the ova peptide SIINFEKL(OT‐I CD8 + T cells) were injected into hosts immediately prior to infection with ova‐peptide expressing L. monocytogenes (Lm‐ova).…”

Section: Tcr Inhibitory Moleculesmentioning

confidence: 99%

“…[11] During acute respiratory viral infection, 3-day old murine neonates have an increased frequency of activated viral specific CD31 + CD8 + T cells within the lung at the peak of the lymphocyte response compared to 7-day old neonates and adults. 85,86 CD31 + neonatal viral-specific CTLs exhibit reduced IFN production and proliferation. 86 CD31 transcript levels are dramatically elevated in sorted CD31 + effector CTLs from neonatally infected mice, which indicate a preferential continued expression in neonatal CTLs, compared to naïve or adult effector T-cell populations.…”

Section: The Role Of the Human Public Tcr Repertoirementioning

confidence: 99%

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Dissecting the defects in the neonatal CD8+ T-cell response

Fike

Kumova

Carey

2019

Journal of Leukocyte Biology

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The neonatal period presents a complex scenario where the threshold of reactivity toward colonizing microbiota, maternal antigens, autoantigens, and pathogens must be carefully moderated and balanced. CD8+ T cells are critical for the response against intracellular bacteria and viruses, but this immune compartment maintains altered function relative to adult counterparts because of the unique challenges which infants face. Here, we review our current understanding of the factors which may promote the attenuation and altered function of the neonatal CD8+ T‐cell response and potential avenues for future study. Specifically, we have focused on the neonatal CD8+ T‐cell ontogeny, memory formation, TCR structure and repertoire, TCR inhibitory receptors, and the clinical implications of altered neonatal CD8+ T‐cell function. Special emphasis has been placed on examining the response of preterm neonates relative to term neonates and adults.

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Section: Tcr Inhibitory Moleculesmentioning

confidence: 99%

Section: Tcr Inhibitory Moleculesmentioning

confidence: 99%

Section: The Role Of the Human Public Tcr Repertoirementioning

confidence: 99%

See 1 more Smart Citation

Dissecting the defects in the neonatal CD8+ T-cell response

Fike

Kumova

Carey

2019

Journal of Leukocyte Biology

Self Cite

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“…The 3-day-old mice neonates are considered representative of late term human neonates of 22-26 weeks gestation [101,102]. Therefore, many infant influenza studies using the mouse model have studied mice in the neonatal phase 2-7 days post-birth which is actually modeling humans in the second trimester of development [102][103][104][105][106]. It has also been reported that the mouse immune makeup at two weeks postpartum most resembles that of the infant human [107], and thus many other infant mice model studies of influenza virus infection have been done at two weeks postpartum [107].…”

Section: Mouse Modelsmentioning

confidence: 99%

The Power of First Impressions: Can Influenza Imprinting during Infancy Inform Vaccine Design?

Rioux¹,

McNeil²,

Francis³

et al. 2020

Preprint

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Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system is thought to synergistically play a role in the increased disease severity in younger age groups. Although vaccines remain the best solution for protecting this vulnerable population, no vaccines are available for those under 6 months, and for infants aged 6 months to 2 years, the vaccine elicits a dampened immune response. Dampened immune responses may be due to unique features of the infant immune system and a lack of pre-existing immunity. Unlike older children and adults, the infant immune system is Th2 skewed and has less antigen presenting cells and soluble immune factors. Paradoxically, we know that a person’s first infection with the influenza virus during infancy or childhood leads to the establishment of life-long immunity toward that particular virus strain. This is called influenza imprinting. To provide better protection against influenza virus infection and disease in infants, more research must be conducted to understand the imprinting event. We contend that by understanding influenza imprinting in the context of the infant immune system and the infant’s immature respiratory tract, we will be able to design more effective influenza vaccines for both infants and adults. Working through the lens of imprinting, using infant influenza animal models such as mice and ferrets, which have proven useful for infant immunity studies, we will gain a better understanding of imprinting and its implications regarding vaccine design. This review examines literature regarding infant immune development, current vaccine strategies, respiratory development, and the importance of researching the imprinting event in infant animal models to develop more effective and protective vaccines for young children.

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“…Respiratory tract inflammatory and infectious disease in infant children represents a significant burden to the healthcare system (1,2). A particular example is influenza virus infection, for which there is evidence of increased incidence of disease severity in infants, as compared to adults in humans and animal models (3,4). Classic theory suggests that adaptive immunity, predominantly the T cell immune response, is altered in infants in order to support self-tolerance, maternal tolerance, and tolerance to new developmental or environmental antigen (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Protective Intranasal Immunization Against Influenza Virus in Infant Mice Is Dependent on IL-6

et al. 2020

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Respiratory diseases adversely affect infants and are the focus of efforts to develop vaccinations and other modalities to prevent disease. The infant immune system differs from that of older children and adults in many ways that are as yet ill understood. We have used a C57BL/6 mouse model of infection with a laboratory-adapted strain of influenza (PR8) to delineate the importance of the cytokine IL-6 in the innate response to primary infection and in the development of protective immunity in adult mice. Herein, we used this same model in infant (14 days of age) mice to determine the effect of IL-6 deficiency. Infant wild type mice are more susceptible than older mice to infection, similar to the findings in humans. IL-6 is expressed in the lung in the early response to PR8 infection. While intramuscular immunization does not protect against lethal challenge, intranasal administration of heat inactivated virus is protective and correlates with expression of IL-6 in the lung, activation of lung CD8 cells, and development of an influenza-specific antibody response. In IL-6 deficient mice, this response is abrogated, and deficient mice are not protected against lethal challenge. These studies support the importance of the role of the tissue environment in infant immunity, and further suggest that IL-6 may be helpful in the generation of protective immune responses in infants.

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Neonatal influenza-specific effector CTLs retain elevated CD31 levels at the site of infection and have decreased IFN-γ production

Cited by 5 publications

References 48 publications

Dissecting the defects in the neonatal CD8+ T-cell response

Dissecting the defects in the neonatal CD8+ T-cell response

The Power of First Impressions: Can Influenza Imprinting during Infancy Inform Vaccine Design?

Protective Intranasal Immunization Against Influenza Virus in Infant Mice Is Dependent on IL-6

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