Lower Functional and Proportional Characteristics of Cord Blood Treg of Male Newborns Compared with Female Newborns

Understanding the early events involved in the induction of immune tolerance to harmless environmental antigens and microbiota compounds could reveal potential targets for allergic disease therapy or prevention. Regulatory T cells (Treg), particularly induced Treg (iTreg), are crucial for the induction and maintenance of tolerance against environmental antigens including allergens. A decrease in the number and/or function of Treg or iTreg could represent an early predictor of allergy development. We analyzed proportional and functional properties of Treg in the cord blood of children of allergic mothers (neonates at high risk of allergy development) and healthy mothers (neonates with relatively low risk of allergy development). We observed a higher number of induced Treg in the cord blood of females compared to males, suggesting an impaired capacity of male immunity to set up tolerance to allergens, which could contribute to the higher incidence of allergy observed in male infants. The decreased proportion of iTreg in cord blood compared with maternal peripheral blood documents the general immaturity of the neonatal immune system. We observed a positive correlation in the demethylation of the Treg-specific demethylated region (TSDR) and the proportion of Treg in cord blood. Our data suggest that immaturity of the neonatal immune system is more severe in males, predisposing them to increased risk of allergy development.

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Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum

Frontiers in Immunology ◽

10.3389/fimmu.2021.714090 ◽

2021 ◽

Vol 12 ◽

Author(s):

Laura S. Peterson ◽

Julien Hedou ◽

Edward A. Ganio ◽

Ina A. Stelzer ◽

Dorien Feyaerts ◽

...

Keyword(s):

T Cells ◽

Immune System ◽

Single Cell ◽

Gestational Age ◽

Immune Cell ◽

Single Cell Analysis ◽

Inflammatory Diseases ◽

Interferon Α ◽

Cytotoxic Lymphocytes ◽

Neonatal Immune System

Although most causes of death and morbidity in premature infants are related to immune maladaptation, the premature immune system remains poorly understood. We provide a comprehensive single-cell depiction of the neonatal immune system at birth across the spectrum of viable gestational age (GA), ranging from 25 weeks to term. A mass cytometry immunoassay interrogated all major immune cell subsets, including signaling activity and responsiveness to stimulation. An elastic net model described the relationship between GA and immunome (R=0.85, p=8.75e-14), and unsupervised clustering highlighted previously unrecognized GA-dependent immune dynamics, including decreasing basal MAP-kinase/NFκB signaling in antigen presenting cells; increasing responsiveness of cytotoxic lymphocytes to interferon-α; and decreasing frequency of regulatory and invariant T cells, including NKT-like cells and CD8+CD161+ T cells. Knowledge gained from the analysis of the neonatal immune landscape across GA provides a mechanistic framework to understand the unique susceptibility of preterm infants to both hyper-inflammatory diseases and infections.

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DISCORDANT RESPONSE OF CD4+ T LYMPHOCYTES TO ANTIRETROVIRAL THERAPY

HIV Infection and Immunosuppressive Disorders ◽

10.22328/2077-9828-2019-11-1-16-30 ◽

2019 ◽

Vol 11 (1) ◽

pp. 16-30 ◽

Cited By ~ 2

Author(s):

K. V. Shmagel

Keyword(s):

Immune Response ◽

T Cells ◽

Viral Load ◽

Immune System ◽

Antiretroviral Therapy ◽

T Lymphocytes ◽

Lymphocyte Proliferation ◽

Immune Reconstitution ◽

Cell Counts ◽

Increased Risk

Antiretroviral therapy (ART) in HIV infected patients generally results in the suppression of viral replication and reconstitution of CD4+ T lymphocytes cell counts. In some patients (about 20%), however, a disturbance in regeneration of immune competent cells with a background of low viral load occurs. The term «immunological nonresponders» has been used to describe this phenomenon. Discordant immune response to antiviral therapy may be caused by increasing of depletion and reducing of production of CD4+ T cells. However, mechanisms for low immune reconstitution are not currently well understood. «Immunological nonresponders» exhibit booster lymphocyte proliferation, increased immune activation and reducing of CD4+ T lymphocytes survival time in comparison with patients with concordant response to the therapy. Their immune system is characterized by more pronounced aging and exhaustion. This leads to early and frequent manifestation of AIDSrelated diseases. Besides, immunological nonresponders have an increased risk of non-AIDS-related diseases due to pronounced systemic inflammation. The objective of the present review was to highlight the important problem that is rather common on аntiretroviral therapy and to enlist the specialists to the solving of this issue.

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Characterization of the Transient Deficiency of PKC Isozyme Levels in Immature Cord Blood T Cells and Its Connection to Anti-Allergic Cytokine Profiles of the Matured Cells

International Journal of Molecular Sciences ◽

10.3390/ijms222312650 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12650

Author(s):

Khalida Perveen ◽

Alex Quach ◽

Michael J. Stark ◽

Susan L. Prescott ◽

Simon C. Barry ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cord Blood ◽

Interleukin 2 ◽

Cell Subset ◽

Necrosis Factor Alpha ◽

Transient Nature ◽

Increased Risk ◽

Pkc Isozymes ◽

Ifn Γ

Cord blood T cells (CBTC) from a proportion of newborns express low/deficient levels of some protein kinase C (PKC) isozymes, with low levels of PKCζ correlating with increased risk of developing allergy and associated decrease in interferon-gamma (IFN-γ) producing T cells. Interestingly, these lower levels of PKCζ were increased/normalized by supplementing women during pregnancy with n-3 polyunsaturated fatty acids. However, at present, we have little understanding of the transient nature of the deficiency in the neonate and how PKCζ relates to other PKC isozymes and whether their levels influence maturation into IFN-γ producing T cells. There is also no information on PKCζ isozyme levels in the T cell subpopulations, CD4+ and CD8+ cells. These issues were addressed in the present study using a classical culture model of neonatal T cell maturation, initiated with phytohaemagglutinin (PHA) and recombinant human interleukin-2 (rhIL-2). Of the isozymes evaluated, PKCζ, β2, δ, μ, ε, θ and λ/ι were low in CBTCs. The PKC isozyme deficiencies were also found in the CD4+ and CD8+ T cell subset levels of the PKC isozymes correlated between the two subpopulations. Examination of changes in the PKC isozymes in these deficient cells following addition of maturation signals showed a significant increase in expression within the first few hours for PKCζ, β2 and μ, and 1–2 days for PKCδ, ε, θ and λ/ι. Only CBTC PKCζ isozyme levels correlated with cytokine production, with a positive correlation with IFN-γ, interleukin (IL)-2 and tumour necrosis factor-alpha (TNF), and a negative association with IL-9 and IL-10. The findings reinforce the specificity in using CBTC PKCζ levels as a biomarker for risk of allergy development and identify a period in which this can be potentially ‘corrected’ after birth.

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The Role of IL-4 Signaling in CD8+ Innate-Like Lymphocyte Development.

Blood ◽

10.1182/blood.v120.21.2161.2161 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2161-2161

Author(s):

Shannon A. Carty ◽

Gary A Koretzky ◽

Martha S Jordan

Keyword(s):

T Cells ◽

Immune System ◽

Organ Culture ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Conflicts Of Interest ◽

Human Umbilical Cord Blood ◽

Human Umbilical Cord ◽

Fetal Thymic Organ Culture

Abstract Abstract 2161 The innate and adaptive arms of the immune system collaborate to protect the host against invading pathogens and perform immune surveillance against malignant transformation. As key effectors of the adaptive immune system, conventional T cells develop in the thymus and exit to the periphery as naïve cells, requiring antigenic stimulation and subsequent differentiation to gain effector functions, such as cytokine secretion or cytolytic activity. In contrast to conventional T cells, non-conventional T lymphocytes possess characteristics of innate immune cells, such as expression of surface markers associated with activation/memory and acquisition of effector function during thymic development, and thus are termed innate-like lymphocytes (ILLs). Recently, an expanded population of CD8+ ILLs was identified in mice with a mutation in the T cell receptor signaling protein SLP-76 (SLP-76 Y145F mice). These CD8+ ILLs are characterized by expression of activation/memory markers CD44 and CD122, the expression of the T-box transcription factor Eomesodermin (Eomes) and rapid production of IFN-γ after ex vivo stimulation. The development of these CD8+ ILLs occurs in a cell-extrinsic manner and requires IL-4. We demonstrate that IL-4 is sufficient to upregulate Eomes expression in wild-type CD8 single-positive (SP) thymocytes in short-term in vitro culture and potentiate CD8+ ILL development in fetal thymic organ culture. Using phospho-flow cytometry, we find that CD8+ ILLs from SLP-76 Y145F mice have increased STAT6 and Akt activation vs. CD8+ non-ILLs. In CD8SP thymocytes deficient in STAT6, Eomes expression is not upregulated in response to IL-4. In addition, we demonstrate that pharmacologic inhibition of Akt in SLP-76 Y145F fetal thymic organ culture blocks CD8+ ILL development and also prevents IL-4 induced Eomes upregulation in WT CD8SP thymocytes. Importantly, we have identified CD8+ ILLs in human fetal thymocytes and umbilical cord blood and found that IL-4 is sufficient to up-regulate Eomes expression in these cells. Taken together, our data suggest that IL-4 signaling via STAT6 and Akt pathways is required for IL-4 induction of Eomes expression and CD8+ ILL development. Understanding signal transduction pathways required for CD8+ ILL development will provide insight into the development of this unique lymphocyte subset that sits at the interface between innate and adaptive immunity and has been identified in human umbilical cord blood. Disclosures: No relevant conflicts of interest to declare.

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Understanding the neonatal immune system: high risk for infection

Critical Care Nurse ◽

10.4037/ccn2001.21.6.35 ◽

2001 ◽

Vol 21 (6) ◽

pp. 35-47 ◽

Cited By ~ 4

Author(s):

WM McKenney

Keyword(s):

Immune System ◽

Newborn Infants ◽

Significant Risk ◽

Systemic Infection ◽

Bacterial Invasion ◽

Postnatal Exposure ◽

Increased Risk ◽

Neonatal Immune System ◽

Hospital Stays ◽

Prolonged Hospital

Neonates are vulnerable to infection from prenatal and postnatal exposure to microorganisms. The immaturity of the immune system in neonates and illness and/or prematurity place these infants at significant risk for bacterial invasion and systemic infection. Long-term sequelae include, but are not limited to, prolonged hospital stays and increased risk of neurodevelopmental problems. Nurses must understand the function of the immune system and the disadvantages unique to newborn infants to be able to provide education to others and appreciate the need for vigilant monitoring and protection of these infants.

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Thymus Growth and Fetal Immune Responses in Diabetic Pregnancies

Hormone and Metabolic Research ◽

10.1055/s-0043-120671 ◽

2017 ◽

Vol 49 (11) ◽

pp. 892-898 ◽

Cited By ~ 1

Author(s):

Katharina Warncke ◽

Ramona Lickert ◽

Stephanie Eitel ◽

Karl-Philipp Gloning ◽

Ezio Bonifacio ◽

...

Keyword(s):

Immune System ◽

Immune Responses ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Maternal Blood ◽

Cell Markers ◽

Cd8 Cells ◽

Maternal Peripheral Blood ◽

Gestational Week

AbstractType 1 diabetes (T1D) during pregnancy possibly affects the development of the thymus and the maturation of the immune system in the offspring. The aim of the ImmunDiabRisk study was to investigate thymus growth and maternal and fetal immune responses in pregnancies with and without T1D. The thymus circumferences of the fetuses of pregnant women with T1D (n=49) and without diabetes (n=59) were measured using ultrasound around the 29th gestational week and standardized for gestational age. Simultaneously, the frequencies and total numbers of cell markers were analyzed by flow cytometry in maternal peripheral blood, and at birth in umbilical cord blood. The standardized circumference of the thymus was similar in fetuses of mothers with and without T1D (p=0.26). We observed higher numbers of FOXP3 Tregs, memory Tregs, erythrocytes, and lymphocytes in the cord blood from T1D pregnancies (p=0.01, p=0.002, p=0.002 and p=0.02, respectively). The frequencies of CD4+/CD8+ T cells correlated positively in maternal blood and umbilical cord blood of mother-child pairs, as did the levels of neutrophils (Spearman’s correlation coefficient r=0.43, p=0.02 for CD4+/CD8+ cells; r=0.46, p=0.03 for neutrophils), while no significant correlations were observed between thymus circumference and any cell markers in the child. Parts of the prenatal immune system seem to develop differently in the offspring of mothers with and without T1D. The correlation of Tregs between maternal blood and cord blood may indicate a significant cross-talk between the maternal and fetal immune system.

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How to Address the Adjuvant Effects of Nanoparticles on the Immune System

Nanomaterials ◽

10.3390/nano10030425 ◽

2020 ◽

Vol 10 (3) ◽

pp. 425 ◽

Cited By ~ 1

Author(s):

Alexia Feray ◽

Natacha Szely ◽

Eléonore Guillet ◽

Marie Hullo ◽

François-Xavier Legrand ◽

...

Keyword(s):

T Cells ◽

Immune System ◽

Human Monocyte ◽

Allergic Diseases ◽

Engineered Nanoparticles ◽

Phenotypic Analysis ◽

Adjuvant Effect ◽

Danger Signals ◽

Set Up

As the nanotechnology market expands and the prevalence of allergic diseases keeps increasing, the knowledge gap on the capacity of nanomaterials to cause or exacerbate allergic outcomes needs more than ever to be filled. Engineered nanoparticles (NP) could have an adjuvant effect on the immune system as previously demonstrated for particulate air pollution. This effect would be the consequence of the recognition of NP as immune danger signals by dendritic cells (DCs). The aim of this work was to set up an in vitro method to functionally assess this effect using amorphous silica NP as a prototype. Most studies in this field are restricted to the evaluation of DCs maturation, generally of murine origin, through a limited phenotypic analysis. As it is essential to also consider the functional consequences of NP-induced DC altered phenotype on T-cells biology, we developed an allogeneic co-culture model of human monocyte-derived DCs (MoDCs) and CD4+ T-cells. We demonstrated that DC: T-cell ratios were a critical parameter to correctly measure the influence of NP danger signals through allogeneic co-culture. Moreover, to better visualize the effect of NP while minimizing the basal proliferation inherent to the model, we recommend testing three different ratios, preferably after five days of co-culture.

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