Characterization of the Highly Prevalent Regulatory CD24hiCD38hi B-Cell Population in Human Cord Blood

Esteve‐Solé, Ana; Teixidó, Irene; Deyà‐Martínez, Àngela; Yagüe, Jordi; Plaza-Martin, Ana María; Juan, Manel; Alsina, Laia

doi:10.3389/fimmu.2017.00201

Cited by 19 publications

(27 citation statements)

References 57 publications

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“…Results obtained after BCG stimulation do not correspond with those published; we have observed no significant differences in IL-12p70 production in comparison with non-exposed infants and an increased production of IL-6. However, from our results and others ( 36 , 44 , 47 – 50 ), it would seem that the immune system of patients with inflammatory diseases and neonates show differentiable characteristics. Also, presence of anti-TNF-a mAbs reduced IL-17 production after BCG stimulation that was rescued after whole-blood washing.…”

Section: Discussionsupporting

confidence: 43%

“…Exposed infants showed an altered T- and B-regulatory compartment. There was an increased Breg frequency, a population having an anti-inflammatory role in cord blood ( 36 ). By contrast, we can speculate that a decreased Treg cell frequency correlating with increased T-cell response to weak stimulus may be a sign of a more responsive immune system, which might be related to the atopy in these patients.…”

Section: Discussionmentioning

confidence: 99%

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Immunological Changes in Blood of Newborns Exposed to Anti-TNF-α during Pregnancy

et al. 2017

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BackgroundAlthough anti-TNF-α monoclonal antibodies are considered safe during pregnancy, there are no studies on the development of the exposed-infant immune system. The objective was to study for the first time the impact of throughout pregnancy exposure to anti-TNF-α has an impact in the development of the infant’s immune system, especially B cells and the IL-12/IFN-γ pathway.MethodsProspective study of infants born to mothers with inflammatory bowel disease treated throughout pregnancy with anti-TNF-α (adalimumab/infliximab). Infants were monitored both clinically and immunologically at birth and at 3, 6, 12, and 18 months.ResultsWe included seven patients and eight healthy controls. Exposed infants had detectable levels of anti-TNF-α until 6 months of age; they presented a more immature B- and helper T-phenotype that normalized within 12 months, with normal immunoglobulin production and vaccine responses. A decreased Treg cell frequency at birth that inversely correlated with mother’s peripartum anti-TNF-α levels was observed. Also, a decreased response after mycobacterial challenge was noted. Clinically, no serious infections occurred during follow-up. Four of seven had atopia.ConclusionThis study reveals changes in the immune system of infants exposed during pregnancy to anti-TNF-α. We hypothesize that a Treg decrease might facilitate hypersensitivity and that defects in IL-12/IFN-γ pathway might place the infant at risk of intracellular infections. Pediatricians should be aware of these changes. Although new studies are needed to confirm these results, our findings are especially relevant in view of a likely increase in the use of these drugs during pregnancy in the coming years.

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Section: Discussionsupporting

confidence: 43%

Section: Discussionmentioning

confidence: 99%

Immunological Changes in Blood of Newborns Exposed to Anti-TNF-α during Pregnancy

et al. 2017

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“…In humans, B reg cells are highly abundant in cord blood, produce IL-10, and are capable of suppressing CD4 T cell responses in an IL-10-dependent manner through CTLA4 and CD40 mechanisms (117). Cord blood B reg cells exhibit higher IgM expression as compared to adult blood and can inhibit both Th1 and Th2 responses (118), however IgM-expressing B cells are more prevalent in infant than in fetal intestines (32). Thus, fetal lymphocytes contribute to the maintenance of tolerance in pregnancy through the generation of T reg and B reg cells.…”

Section: Cell-extrinsic Mechanismsmentioning

confidence: 99%

Mechanisms of Fetal T Cell Tolerance and Immune Regulation

2020

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The developing human fetus generates both tolerogenic and protective immune responses in response to the unique requirements of gestation. Thus, a successful human pregnancy depends on a fine balance between two opposing immunological forces: the semi-allogeneic fetus learns to tolerate both self-and maternal-antigens and, in parallel, develops protective immunity in preparation for birth. This critical window of immune development bridges prenatal immune tolerance with the need for postnatal environmental protection, resulting in a vulnerable neonatal period with heightened risk of infection. The fetal immune system is highly specialized to mediate this transition and thus serves a different function from that of the adult. Adaptive immune memory is already evident in the fetal intestine. Fetal T cells with pro-inflammatory potential are born in a tolerogenic environment and are tightly controlled by both cell-intrinsic and-extrinsic mechanisms, suggesting that compartmentalization and specialization, rather than immaturity, define the fetal immune system. Dysregulation of fetal tolerance generates an inflammatory response with deleterious effects to the pregnancy. This review aims to discuss the recent advances in our understanding of the cellular and molecular composition of fetal adaptive immunity and the mechanisms that govern T cell development and function. We also discuss the tolerance promoting environment that impacts fetal immunity and the consequences of its breakdown. A greater understanding of fetal mechanisms of immune activation and regulation has the potential to uncover novel paradigms of immune balance which may be leveraged to develop therapies for transplantation, autoimmune disease, and birth-associated inflammatory pathologies.

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“…This population also tends to have an overall higher number of circulating T and B cells that decreases drastically by six years of age [108]. An increase in regulatory T and B cells is also noted in neonatal blood samples [109][110][111][112][113]. Despite the increase in the frequency of regulatory T cells in neonatal blood, the functional ability of neonatal regulatory T cells to suppress dendritic cell function and to blunt the immune reaction is diminished relative to adults [114].…”

Section: The Pediatric Immune System Is Different Than That Of the Adultmentioning

confidence: 99%

The Importance of Vaccinating Children and Pregnant Women against Influenza Virus Infection

Misra

Nayak

2019

Pathogens

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Influenza virus infection is responsible for significant morbidity and mortality in the pediatric and pregnant women populations, with deaths frequently caused by severe influenza-associated lower respiratory tract infection and acute respiratory distress syndrome (ARDS). An appropriate immune response requires controlling the viral infection through activation of antiviral defenses, which involves cells of the lung and immune system. High levels of viral infection or high levels of inflammation in the lower airways can contribute to ARDS. Pregnant women and young children, especially those born prematurely, may develop serious complications if infected with influenza virus. Vaccination against influenza will lead to lower infection rates and fewer complications, even if the vaccine is poorly matched to circulating viral strains, with maternal vaccination offering infants protection via antibody transmission through the placenta and breast milk. Despite the health benefits of the influenza vaccine, vaccination rates around the world remain well below targets. Trust in the use of vaccines among the public must be restored in order to increase vaccination rates and decrease the public health burden of influenza.

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Characterization of the Highly Prevalent Regulatory CD24hiCD38hi B-Cell Population in Human Cord Blood

Cited by 19 publications

References 57 publications

Immunological Changes in Blood of Newborns Exposed to Anti-TNF-α during Pregnancy

Immunological Changes in Blood of Newborns Exposed to Anti-TNF-α during Pregnancy

Mechanisms of Fetal T Cell Tolerance and Immune Regulation

The Importance of Vaccinating Children and Pregnant Women against Influenza Virus Infection

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