tetano
Editor, Senior Moderator
J Leukoc Biol. 2016 Jan 28. pii: jlb.4A1014-497RR. [Epub ahead of print]
[h=1]Control of influenza infection is impaired by diminished interferon-γ secretion by CD4 T cell in the lungs of toddlers.[/h] Verhoeven D[SUP]1[/SUP], Perry S[SUP]2[/SUP], Pryharski K[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Respiratory viral infections, such as influenza, can lead to delayed viral clearance in toddlers, possibly exacerbating disease morbidity. We hypothesized that defective CD4 T cells in toddlers may contribute to a failure to clear virus at a similar rate to adults. Thus, we developed a young mouse model to examine potential divergent responses between toddlers and adults. We determined that young mice (toddler mice, 21 d old) were actively generating and recruiting effector/memory T cells, whereas memory populations were firmly established in older, adult mice (8-10 wk old). We infected toddler and adult mice with influenza A/PR8/34 (H1N1) and found young mice had elevated morbidity, as measured by enhanced weight loss and lower partial pressure of oxygen levels, throughout the infection, thus, modeling the higher morbidity observed in children (<2 y old) during infection. Early viral loads were comparable to adult mice, but toddler mice failed to clear virus by 10 d postinfection. This delayed clearance corresponded to poor lung recruitment of CD4 T cells, lower antiviral T cell responses, and lower B cell/antibodies in the lungs. Mechanistically, diminished interferon-γ was detected in the lungs of toddler mice throughout the infection and corresponded to intrinsic, rather than extrinsic, CD4 T cell limitations in interferon-γ transcription. Moreover, defects in interferon-γ production appeared downstream from signal transducer and activator of transcription 4 in the interleukin-12 signaling pathway, suggesting maturational delays different from neonates. Importantly, recombinant interferon-γ supplementation rescued CD4 T cell numbers in the lungs and influenza-specific antibody formation. This study highlights the intrinsic limitations in CD4 T cell effector functions that may arise in toddlers and contribute to disease pathology.
? Society for Leukocyte Biology.
[h=4]KEYWORDS:[/h] cytokine responses; influenza virus; pediatric immunology
PMID: 26823488 [PubMed - as supplied by publisher]
[h=1]Control of influenza infection is impaired by diminished interferon-γ secretion by CD4 T cell in the lungs of toddlers.[/h] Verhoeven D[SUP]1[/SUP], Perry S[SUP]2[/SUP], Pryharski K[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Respiratory viral infections, such as influenza, can lead to delayed viral clearance in toddlers, possibly exacerbating disease morbidity. We hypothesized that defective CD4 T cells in toddlers may contribute to a failure to clear virus at a similar rate to adults. Thus, we developed a young mouse model to examine potential divergent responses between toddlers and adults. We determined that young mice (toddler mice, 21 d old) were actively generating and recruiting effector/memory T cells, whereas memory populations were firmly established in older, adult mice (8-10 wk old). We infected toddler and adult mice with influenza A/PR8/34 (H1N1) and found young mice had elevated morbidity, as measured by enhanced weight loss and lower partial pressure of oxygen levels, throughout the infection, thus, modeling the higher morbidity observed in children (<2 y old) during infection. Early viral loads were comparable to adult mice, but toddler mice failed to clear virus by 10 d postinfection. This delayed clearance corresponded to poor lung recruitment of CD4 T cells, lower antiviral T cell responses, and lower B cell/antibodies in the lungs. Mechanistically, diminished interferon-γ was detected in the lungs of toddler mice throughout the infection and corresponded to intrinsic, rather than extrinsic, CD4 T cell limitations in interferon-γ transcription. Moreover, defects in interferon-γ production appeared downstream from signal transducer and activator of transcription 4 in the interleukin-12 signaling pathway, suggesting maturational delays different from neonates. Importantly, recombinant interferon-γ supplementation rescued CD4 T cell numbers in the lungs and influenza-specific antibody formation. This study highlights the intrinsic limitations in CD4 T cell effector functions that may arise in toddlers and contribute to disease pathology.
? Society for Leukocyte Biology.
[h=4]KEYWORDS:[/h] cytokine responses; influenza virus; pediatric immunology
PMID: 26823488 [PubMed - as supplied by publisher]