Neonatal immunity: faulty T-helpers and the shortcomings of dendritic cells

Zaghouani, Habib; Hoeman, Christine; Adkins, Becky

doi:10.1016/j.it.2009.09.002

Cited by 219 publications

(221 citation statements)

References 52 publications

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“…This suppression is much more potent for Th1 than for Th2-type cytokine production by cord blood cells, consistent with generally Th2 cytokine bias of cord blood lymphocytes (18,63,64). IL-10 or TGF-b do not mediate this T reg suppression, consistent with some but not all prior studies (36,38).…”

Section: Cd4supporting

confidence: 82%

Human Cord Blood CD4+CD25hi Regulatory T Cells Suppress Prenatally Acquired T Cell Responses toPlasmodium falciparumAntigens

Mackroth

Malhotra

Mungai

et al. 2011

The Journal of Immunology

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In malaria endemic regions, a fetus is often exposed in utero to Plasmodium falciparum blood-stage Ags. In some newborns, this can result in the induction of immune suppression. We have previously shown these modulated immune responses to persist postnatally, with a subsequent increase in a child’s susceptibility to infection. To test the hypothesis that this immune suppression is partially mediated by malaria-specific regulatory T cells (Tregs) in utero, cord blood mononuclear cells (CBMC) were obtained from 44 Kenyan newborns of women with and without malaria at delivery. CD4+CD25lo T cells and CD4+CD25hi FOXP3+ cells (Tregs) were enriched from CBMC. Treg frequency and HLA-DR expression on Tregs were significantly greater for Kenyan as compared with North American CBMC (p < 0.01). CBMC/CD4+ T cells cultured with P. falciparum blood-stage Ags induced production of IFN-γ, IL-13, IL-10, and/or IL-5 in 50% of samples. Partial depletion of CD25hi cells augmented the Ag-driven IFN-γ production in 69% of subjects with malaria-specific responses and revealed additional Ag-reactive lymphocytes in previously unresponsive individuals (n = 3). Addition of Tregs to CD4+CD25lo cells suppressed spontaneous and malaria Ag-driven production of IFN-γ in a dose-dependent fashion, until production was completely inhibited in most subjects. In contrast, Tregs only partially suppressed malaria-induced Th2 cytokines. IL-10 or TGF-β did not mediate this suppression. Thus, prenatal exposure to malaria blood-stage Ags induces Tregs that primarily suppress Th1-type recall responses to P. falciparum blood-stage Ags. Persistence of these Tregs postnatally could modify a child’s susceptibility to malaria infection and disease.

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Section: Cd4supporting

confidence: 82%

Human Cord Blood CD4+CD25hi Regulatory T Cells Suppress Prenatally Acquired T Cell Responses toPlasmodium falciparumAntigens

Mackroth

Malhotra

Mungai

et al. 2011

The Journal of Immunology

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“…An adaptive immune response is essentially lacking because the newborn immune system has no memory, leaving the newborn dependent on innate immune defence mechanisms. It has long been established that infants are born with a T-helper cell (Th) type 2 bias due to a limited capacity to produce Th1 cytokines [14]. Although most cell types are present in normal concentrations in the newborn's blood, they lack the capacity to mount adult-like Th1 instructive signals, and to produce interleukin (IL)-12 p70 in particular [15].…”

Section: Early Immune Maturation and Respiratory Healthmentioning

confidence: 99%

Early-life origins of chronic respiratory diseases: understanding and promoting healthy ageing

et al. 2014

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Chronic obstructive respiratory disorders such as asthma and chronic obstructive pulmonary disease often originate early in life. In addition to a genetic predisposition, prenatal and early-life environmental exposures have a persistent impact on respiratory health. Acting during a critical phase of lung development, these factors may change lung structure and metabolism, and may induce maladaptive responses to harmful agents, which will affect the whole lifespan.Some environmental factors, such as exposure to cigarette smoke, type of childbirth and diet, may be modifiable, but it is more difficult to influence other factors, such as preterm birth and early exposure to viruses or allergens.Here, we bring together recent literature to analyse the critical aspects involved in the early stages of lung development, going back to prenatal and perinatal events, and we discuss the mechanisms by which noxious factors encountered early on may have a lifelong impact on respiratory health.We briefly comment on the need for early disease biomarkers and on the possible role of ''-omic'' technologies in identifying risk profiles predictive of chronic respiratory conditions. Such profiles could guide the ideation of effective preventive strategies and/or targeted early lifestyle or therapeutic interventions. @ERSpublications Early-life factors have a role in onset of asthma and COPD; early postnatal interventions may promote lung health http://ow.ly/BvUrx

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“…In the current study, we investigated the role of DNA methylation and its association with patterns of gene expression under two scenarios: (1) during the steady-state development of naive CD4 þ T-cells shortly after birth; (2) following the activation of T-cells during entry into the cell cycle. Our data provide insights into the molecular pathways of early T-cell programming, and characterize developmental pathways potentially susceptible to disruption through early-life environmental exposures.…”

Section: Introductionmentioning

confidence: 99%

Genome-scale profiling reveals a subset of genes regulated by DNA methylation that program somatic T-cell phenotypes in humans

et al. 2012

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The aim of this study was to investigate the dynamics and relationship between DNA methylation and gene expression during early T-cell development. Mononuclear cells were collected at birth and at 12 months from 60 infants and were either activated with anti-CD3 for 24 h or cultured in media alone, and the CD4 þ T-cell subset purified. DNA and RNA were co-harvested and DNA methylation was measured in 450 000 CpG sites in parallel with expression measurements taken from 25 000 genes. In unstimulated cells, we found that a subset of 1188 differentially methylated loci were associated with a change in expression in 599 genes (adjusted P valueo0.01, b-fold 40.1). These genes were enriched in reprogramming regions of the genome known to control pluripotency. In contrast, over 630 genes were induced following low-level T-cell activation, but this was not associated with any significant change in DNA methylation. We conclude that DNA methylation is dynamic during early T-cell development, and has a role in the consolidation of T-cell-specific gene expression. During the early phase of clonal expansion, DNA methylation is stable and therefore appears to be of limited importance in short-term T-cell responsiveness.

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Neonatal immunity: faulty T-helpers and the shortcomings of dendritic cells

Cited by 219 publications

References 52 publications

Human Cord Blood CD4+CD25hi Regulatory T Cells Suppress Prenatally Acquired T Cell Responses toPlasmodium falciparumAntigens

Human Cord Blood CD4+CD25hi Regulatory T Cells Suppress Prenatally Acquired T Cell Responses toPlasmodium falciparumAntigens

Early-life origins of chronic respiratory diseases: understanding and promoting healthy ageing

Genome-scale profiling reveals a subset of genes regulated by DNA methylation that program somatic T-cell phenotypes in humans

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