Significant augmentation of regulatory T cell numbers occurs during the early neonatal period

Hayakawa, Seiichi; Ohno, Norioki; Okada, Satoshi; Kobayashi, Masao

doi:10.1111/cei.13008

Cited by 37 publications

(40 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5D). Our observation differs from findings in non-polarised conditions: In cord blood, suppressive Tregs were found increased compared to adult blood in the early phase after birth 43 and may expand under inflammatory conditions, e.g. necrotizing enterocolitis (NEC) 44 .…”

Section: Discussioncontrasting

confidence: 99%

Impaired functional capacity of polarised neonatal macrophages

Dreschers

Ohl

Schulte

et al. 2020

Sci Rep

View full text Add to dashboard Cite

neonatal sepsis is accompanied by impaired apoptotic depletion of monocytes and macrophages (MΦ), aberrant cytokine production, impaired cell metabolism, and sustained inflammation. Macrophage-colony stimulating factor (M-CSF) triggers the differentiation from monocytes into MΦ (MΦ-0). Interleukin-10 (IL10) and Interferon-gamma (IFNy) further differentiate MΦ subpopulations, the anti-inflammatory MΦ-IL10 and the pro-inflammatory MΦ-ifny subtype. We previously have shown significant differences between adult (PBMΦ) and cord blood (CBMΦ) in the metabolism of all subtypes. To test the hypothesis whether the competence to differentiate monocytes into MΦ-0 and to polarise into MΦ-ifny and MΦ-IL10 was diminished in CBMΦ as compared to PBMΦ, we polarised monocytes by cultivation with M-CSF for 72 h, followed by stimulation with IFNy or IL10, for 48 h. After flow cytometry based immunotyping, we tested four functions: Phagocytosis of GFP-E. coli, uptake of erythrocytes, t-cell proliferation, induction of regulatory t-cells as well as phosphorylation analysis of AKT and STAT1/STAT3. Phosphorylation of STAT-1 and STAT-3, obligatory to differentiate into MΦifnγ, MΦ-0 and MΦ-IL10, was found to be aberrant in CBMΦ. Whereas infected MΦ-0 showed identical phagocytic indices and intracellular degradation, TLR4-expression, NFkB up-regulation, IL10-, IL6-, and tnfα production of CBMΦ-0 were reduced. In addition, the capacity to bind aged erythrocytes and the consecutive IL10 production was lower in CBMΦ-IL10. Polarised PBMΦ-IFNy and PBMΦ-IL10 expressed higher levels of co-stimulatory receptors (CD80, CD86), had a higher capacity to stimulate T-cells and induced higher amounts of regulatory t-cells (all p < 0.05 vs. corresponding CBMΦ). Hypoxia-induciblefactor-1α (HIF-1α) was stronger expressed in CBMΦ-IFNy and upregulated in infected CBMΦ-0, whereas heme-oxygenase 1 (HO-1) expression was similar to adult PBMΦ. neonatal MΦ-0, MΦ-ifny and MΦ-IL10 polarisation is impaired with respect to phenotype and functions tested which may contribute to sustained inflammation in neonatal sepsis. Macrophages (MФ) have an extremely broad spectrum of functions in both the induction and resolution of inflammation due to their heterogeneity and plasticity. They are involved in a range of processes, including tissue homeostasis, clearance or pulmonary surfactant as well as inflammation. Deriving from monocytes, they develop into different populations of circulating inflammatory or resident macrophages (MФ) recruited to various tissues. These processes occur in response to inflammation or infection but also in homeostasis in order to replace apoptotic (MФ) 1. The migration of monocytes to the site of infection is crucial 2. After infiltrating the infected tissue they polarise into functional distinguishable MФ. The term "polarisation" instead of differentiation became accepted, since this process depends on the local cytokine milieu and specific microenvironmental cues, and therefore is reversible 3,4. By analogy to T helper cell (Th) nomenclature, MФ ...

show abstract

Section: Discussioncontrasting

confidence: 99%

Impaired functional capacity of polarised neonatal macrophages

Dreschers

Ohl

Schulte

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In early life, the immune system is uniquely skewed toward tolerance to avoid development of autoimmune responses and to discriminate commensal organisms from pathogens (12)(13)(14)(15)(16). Information currently available about pediatric immunological development mainly derives from studies using the mouse model or human cord blood, both of which have limited translational applications (17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Clinical and Immunological Metrics During Pediatric Rhesus Macaque Development

et al. 2020

View full text Add to dashboard Cite

Background: Clinical measurements commonly used to evaluate overall health of laboratory animals including complete blood count, serum chemistry, weight, and immunophenotyping, differ with respect to age, development, and environment. This report provides comprehensive clinical and immunological reference ranges for pediatric rhesus macaques over the first year of life. Methods: We collected and analyzed blood samples from 151 healthy rhesus macaques, aged 0-55 weeks, and compared mother-reared infants to two categories of nursery-reared infants; those on an active research protocol and those under derivation for the expanded specific-pathogen-free breeding colony. Hematology was performed on EDTA-anticoagulated blood using a Sysmex XT2000i, and serum clinical chemistry was performed using the Beckman AU480 chemistry analyzer. Immunophenotyping of whole blood was performed with immunofluorescence staining and subsequent flow cytometric analysis on a BD LSRFortessa. Plasma cytokine analysis was performed using a Millipore multiplex Luminex assay. Results: For hematological and chemistry measurements, pediatric reference ranges deviate largely from adults. Comparison of mother-reared and nursery-reared animals revealed that large differences depend on rearing conditions and diet. Significant differences found between two nursery-reared cohorts (research and colony animals) indicate large influences of experimental factors and anesthetic events on these parameters. Immune cells and cytokine responses presented with distinct patterns for infants depending on age, birth location, and rearing conditions. Conclusions: Our results illustrate how the immune system changed over time and that there was variability among pediatric age groups. Reference ranges of results reported here will support interpretations for how infection and treatment may skew common immune correlates used for assessment of pathology or protection in research studies as well as help veterinarians in the clinical care of infant non-human primates. We highlighted Merino et al. Clinical Immunology of Infant Macaques the importance of using age-specific reference comparisons for pediatric studies and reiterated the utility of rhesus macaques as a model for human studies. Given the rapid transformation that occurs in multiple tissue compartments after birth and cumulative exposures to antigens as individuals grow, a better understanding of immunological development and how this relates to timing of infection or vaccination will support optimal experimental designs for developing vaccines and treatment interventions.

show abstract

“…As if these hurdles were not high enough, we have an increasing appreciation for the heightened T regulatory cell (T reg ) response that is present in newborns and young infants. Studies in human infants reveal a higher representation of Tregs in circulation ( 53 – 59 ), a finding also seen in NHP [( 60 ) and manuscript in press ]. This may be the result of the enhanced propensity for cells to differentiate into Tregs in these individuals ( 59 , 61 – 63 ).…”

Section: The Infant Immune Systemmentioning

confidence: 71%

Challenges for the Newborn Following Influenza Virus Infection and Prospects for an Effective Vaccine

Alexander-Miller

2020

Front. Immunol.

View full text Add to dashboard Cite

Newborns are at significantly increased risk of severe disease following infection with influenza virus. This is the collective result of their naïve status, altered immune responsiveness, and the lack of a vaccine that is effective in these individuals. Numerous studies have revealed impairments in both the innate and adaptive arms of the immune system of newborns. The consequence of these alterations is a quantitative and qualitative decrease in both antibody and T cell responses. This review summarizes the hurdles newborns experience in mounting an effective response that can clear influenza virus and limit disease following infection. In addition, the challenges, as well as the opportunities, for developing vaccines that can elicit protective responses in these at risk individuals are discussed.

show abstract

Significant augmentation of regulatory T cell numbers occurs during the early neonatal period

Cited by 37 publications

References 39 publications

Impaired functional capacity of polarised neonatal macrophages

Impaired functional capacity of polarised neonatal macrophages

Clinical and Immunological Metrics During Pediatric Rhesus Macaque Development

Challenges for the Newborn Following Influenza Virus Infection and Prospects for an Effective Vaccine

Contact Info

Product

Resources

About