Neonatal thymectomy reveals differentiation and plasticity within human naive T cells

Broek, Theo van den; Delemarre, Eveline M.; Janssen, Willemijn J.M.; Nievelstein, Rutger A.J.; Broen, Jasper; Tesselaar, Kiki; Borghans, José A. M.; Nieuwenhuis, Edward E.S.; Prakken, Berent J.; Mokrý, Michal; Jansen, Nicolaas J. G.; Wijk, Femke van

doi:10.1172/jci84997

Cited by 83 publications

(113 citation statements)

References 50 publications

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“…In addition, a large proportion of human naïve neonatal T cells are able to produce the CXCL8 chemokine upon stimulation [34]. The production of CXCL8 by neonatal T cells is unique in that it occurs in absence of effector differentiation, specifically in CD31 T cells that have recently emerged from the thymus [35]. Consistent with an innate-like phenotype of these, production of CXCL8 is enhanced by co-activation of extracellular PRRs.…”

Section: Box 2 Relative Importance Of the Innate And Adaptive Immune mentioning

confidence: 99%

An Immunological Perspective on Neonatal Sepsis

Kan

Razzaghian

Lavoie

2016

Trends in Molecular Medicine

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Despite concerted international efforts, mortality from neonatal infections remains unacceptably high in some areas of the world, particularly for premature infants. Recent developments in flow cytometry and next-generation sequencing technologies have led to major discoveries over the past few years, providing a more integrated understanding of the developing human immune system in the context of its microbial environment. We review these recent findings, focusing on how in human newborns incomplete maturation of the immune system before a full term of gestation impacts on their vulnerability to infection. We also discuss some of the clinical implications of this research in guiding the design of more-accurate age-adapted diagnostic and preventive strategies for neonatal sepsis.

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Section: Box 2 Relative Importance Of the Innate And Adaptive Immune mentioning

confidence: 99%

An Immunological Perspective on Neonatal Sepsis

Kan

Razzaghian

Lavoie

2016

Trends in Molecular Medicine

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“…Naïve CD4 + T-cells are usually seen as a homogeneous population regarding stage of maturation and cell differentiation, although their phenotypic and functional variety is increasingly recognized (13, 15, 16, 18, 19). Next, we overview the main factors contributing to this heterogeneity, as well as the principal subpopulations identified.…”

Section: Naïve Cd4+ T-cell Heterogeneitymentioning

confidence: 99%

“…The functional properties of naïve CD4 + T-cells change along infancy, with a clear trend to differentiation into a Th2 profile of cytokine production in early life (125, 126). Additionally, thymic-generated functional populations that are hardly found beyond the first decade of life have been described with a yet unclear role in immunity, as illustrated by the IL-8-producing subset (15, 18). …”

Section: Naïve Cd4+ T-cell Heterogeneitymentioning

confidence: 99%

“…Finally, the human naïve CD4 + T-cell compartment has been recently shown to include a small population of memory cells (<1%), as attested by rapid interferon-γ production upon TCR stimulation, which could be identified by the expression of Fas (CD95) and β-chain of the IL-2 receptor (CD122), in the absence of CD45RO (17, 18). These so-called memory-stem cells are generated during primary immune responses and are considered a reservoir for the memory pool, in line with their unique ability to self-renew through still unclear mechanisms (17).…”

Section: Naïve Cd4+ T-cell Heterogeneitymentioning

confidence: 99%

“…We further outline the cumulative evidence pointing to age-dependent maturation processes in the periphery that may alter the cell threshold to homeostatic cues (2, 10–14). Finally, the existence of phenotypic/functional naïve CD4 + T-cell subpopulations with distinct homeostasis is reviewed (13, 15–18), with a particular focus on thymic-derived regulatory T-cells (naïve-Tregs) that given their high self-reactivity are considered essential to prevent autoimmunity (19, 20). This suppressive lineage, defined by FOXP3 expression, has recently been shown to rely on unique homeostatic requirements (19, 21).…”

Section: Introduction and Aimmentioning

confidence: 99%

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Establishment and Maintenance of the Human Naïve CD4+ T-Cell Compartment

Silva¹,

Sousa

2016

Front. Pediatr.

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The naïve CD4+ T-cell compartment is considered essential to guarantee immune competence throughout life. Its replenishment with naïve cells with broad diverse receptor repertoire, albeit with reduced self-reactivity, is ensured by the thymus. Nevertheless, cumulative data support a major requirement of post-thymic proliferation both for the establishment of the human peripheral naïve compartment during the accelerated somatic growth of childhood, as well as for its lifelong maintenance. Additionally, a dynamic equilibrium is operating at the cell level to fine-tune the T-cell receptor threshold to activation and survival cues, in order to counteract the continuous naïve cell loss by death or conversion into memory/effector cells. The main players in these processes are low-affinity self-peptide/MHC and cytokines, particularly IL-7. Moreover, although naïve CD4+ T-cells are usually seen as a homogeneous population regarding stage of maturation and cell differentiation, increasing evidence points to a variety of phenotypic and functional subsets with distinct homeostatic requirements. The paradigm of cells committed to a distinct lineage in the thymus are the naïve regulatory T-cells, but other functional subpopulations have been identified based on their time span after thymic egress, phenotypic markers, such as CD31, or cytokine production, namely IL-8. Understanding the regulation of these processes is of utmost importance to promote immune reconstitution in several clinical settings, namely transplantation, persistent infections, and aging. In this mini review, we provide an overview of the mechanisms underlying human naïve CD4+ T-cell homeostasis, combining clinical data, experimental studies, and modeling approaches.

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Recent Advancements in Regenerative Approaches for Thymus Rejuvenation

Sharma

Moroni

2021

Advanced Science

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The thymus plays a key role in adaptive immunity by generating a diverse population of T cells that defend the body against pathogens. Various factors from disease and toxic insults contribute to the degeneration of the thymus resulting in a fewer output of T cells. Consequently, the body is prone to a wide host of diseases and infections. In this review, first, the relevance of the thymus is discussed, followed by thymic embryological organogenesis and anatomy as well as the development and functionality of T cells. Attempts to regenerate the thymus include in vitro methods, such as forming thymic organoids aided by biofabrication techniques that are transplantable. Ex vivo methods that have shown promise in enhancing thymic regeneration are also discussed. Current regenerative technologies have not yet matched the complexity and functionality of the thymus. Therefore, emerging techniques that have shown promise and the challenges that lie ahead are explored.

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Neonatal thymectomy reveals differentiation and plasticity within human naive T cells

Cited by 83 publications

References 50 publications

An Immunological Perspective on Neonatal Sepsis

An Immunological Perspective on Neonatal Sepsis

Establishment and Maintenance of the Human Naïve CD4+ T-Cell Compartment

Recent Advancements in Regenerative Approaches for Thymus Rejuvenation

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