The human fetal thymus generates invariant effector γδ T cells

Tieppo, Paola; Papadopoulou, Maria V.; Gatti, Deborah; McGovern, Naomi; Chan, Jerry Kok Yen; Gosselin, Françoise; Goetgeluk, Glenn; Weening, Karin; Ma, Lifang; Dauby, Nicolás; Cogan, Alexandra; Donner, Cathérine; Ginhoux, Florent; Vandekerckhove, Bart; Vermijlen, David

doi:10.1084/jem.20190580

Cited by 65 publications

(154 citation statements)

References 90 publications

(138 reference statements)

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“…The earliest T cells, namely the subset of pAg-specific Vγ9Vδ2 + T cells, are followed by Vδ1 + T cells that can be detected in fetal blood at week 25 and increase to become the major population of γδ T cells at term-delivery [37,62,67] (Figure 1). The γδ TCR repertoire of fetal non-Vγ9Vδ2 + thymocytes was shown to comprise an oligoclonal TRG repertoire, a diverse TRGV usage (including the non-functional TRGV10) and usage of mainly TRDV2 rearrangements paired with TRDJ2 or TRDJ3 [36]. Those fetal thymocytes use few N insertions, and TdT expression at this stage is low [36].…”

Section: γδ T Cell Subsets Arise Early During Ontogenymentioning

confidence: 99%

“…The γδ TCR repertoire of fetal non-Vγ9Vδ2 + thymocytes was shown to comprise an oligoclonal TRG repertoire, a diverse TRGV usage (including the non-functional TRGV10) and usage of mainly TRDV2 rearrangements paired with TRDJ2 or TRDJ3 [36]. Those fetal thymocytes use few N insertions, and TdT expression at this stage is low [36]. Similar to germline-encoded Vγ9JP rearrangements, invariant TCRs (TRGV8JP1, TRGV10JP1, TRDV2D3, TRDV1D3) were found to be expressed by fetal non-Vγ9Vδ2 + thymocytes, and recombination is thought to be similarly dictated by short homology repeats [36].…”

Section: γδ T Cell Subsets Arise Early During Ontogenymentioning

confidence: 99%

“…Those fetal thymocytes use few N insertions, and TdT expression at this stage is low [36]. Similar to germline-encoded Vγ9JP rearrangements, invariant TCRs (TRGV8JP1, TRGV10JP1, TRDV2D3, TRDV1D3) were found to be expressed by fetal non-Vγ9Vδ2 + thymocytes, and recombination is thought to be similarly dictated by short homology repeats [36]. Using OP9DL1 cultures, Tieppo and colleagues showed the involvement of Lin28b in the induction of an effector program, the inhibition of TdT expression and the formation of germline-encoded CDR3γ and δ sequences in fetal thymocytes.…”

Section: γδ T Cell Subsets Arise Early During Ontogenymentioning

confidence: 99%

“…The TCR repertoires of postnatal thymic non-Vγ9Vδ2 + T cells, mostly Vδ1 + , have been reported to be extremely polyclonal [36,69,70]. In the thymus, postnatal Vδ1 + T cells use various TRGV gene segments, yet with a distinct preference for TRGJ1.…”

Section: Development and Maintenance Of γδ T Cells In Child-and Adultmentioning

confidence: 99%

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Human γδ TCR Repertoires in Health and Disease

Fichtner

Ravens

Prinz

2020

Cells

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The T cell receptor (TCR) repertoires of γδ T cells are very different to those of αβ T cells. While the theoretical TCR repertoire diversity of γδ T cells is estimated to exceed the diversity of αβ T cells by far, γδ T cells are still understood as more invariant T cells that only use a limited set of γδ TCRs. Most of our current knowledge of human γδ T cell receptor diversity builds on specific monoclonal antibodies that discriminate between the two major subsets, namely Vδ2+ and Vδ1+ T cells. Of those two subsets, Vδ2+ T cells seem to better fit into a role of innate T cells with semi-invariant TCR usage, as compared to an adaptive-like biology of some Vδ1+ subsets. Yet, this distinction into innate-like Vδ2+ and adaptive-like Vδ1+ γδ T cells does not quite recapitulate the full diversity of γδ T cell subsets, ligands and interaction modes. Here, we review how the recent introduction of high-throughput TCR repertoire sequencing has boosted our knowledge of γδ T cell repertoire diversity beyond Vδ2+ and Vδ1+ T cells. We discuss the current understanding of clonal composition and the dynamics of human γδ TCR repertoires in health and disease.

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Section: γδ T Cell Subsets Arise Early During Ontogenymentioning

confidence: 99%

Section: γδ T Cell Subsets Arise Early During Ontogenymentioning

confidence: 99%

Section: γδ T Cell Subsets Arise Early During Ontogenymentioning

confidence: 99%

Section: Development and Maintenance Of γδ T Cells In Child-and Adultmentioning

confidence: 99%

See 2 more Smart Citations

Human γδ TCR Repertoires in Health and Disease

Fichtner

Ravens

Prinz

2020

Cells

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“…γδ TCR gene rearrangement can be detected by embryonic day 14 in the mouse thymus, week 8 in humans, and canonical subsets can also be detected extrathymically in both species during fetal development [111][112][113]. In the human fetus, the Vγ9+Vδ2+ subset is among the first T cell subset to be developed and this population further expands during childhood, although these cells have a distinct lineage, as recent studies have shown that the ontogeny between fetal blood γδ and adult blood γδ is dissimilar [112,[114][115][116]. Vγ9 and Vδ2 V gene segments can be detected as early as 5 to 6 weeks gestation in the fetal liver and after 8 weeks in the fetal thymus [117].…”

Section: In Humansmentioning

confidence: 99%

The Aging of γδ T Cells

Lau

Fülöp

et al. 2020

Cells

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In the coming decades, many developed countries in the world are expecting the "greying" of their populations. This phenomenon poses unprecedented challenges to healthcare systems. Aging is one of the most important risk factors for infections and a myriad of diseases such as cancer, cardiovascular and neurodegenerative diseases. A common denominator that is implicated in these diseases is the immune system. The immune system consists of the innate and adaptive arms that complement each other to provide the host with a holistic defense system. While the diverse interactions between multiple arms of the immune system are necessary for its function, this complexity is amplified in the aging immune system as each immune cell type is affected differently-resulting in a conundrum that is especially difficult to target. Furthermore, certain cell types, such as γδ T cells, do not fit categorically into the arms of innate or adaptive immunity. In this review, we will first introduce the human γδ T cell family and its ligands before discussing parallels in mice. By covering the ontogeny and homeostasis of γδ T cells during their lifespan, we will better capture their evolution and responses to age-related stressors. Finally, we will identify knowledge gaps within these topics that can advance our understanding of the relationship between γδ T cells and aging, as well as age-related diseases such as cancer.Their well-characterized roles further imply the physiological importance of age-associated T-cell adaptations, which garners the widespread scientific interest that has contributed to the current depth of T-cell-related investigations [14,15].T cells can essentially be classified into the adaptive arm, although minority subsets exhibit an innate phenotype. Adaptive T cells include those expressing an αβ T cell receptor (TCR) at their surface and "innate-like" T cells are comprised of T cells expressing a γδ TCR, mucosal associated invariant T (MAIT), invariant natural killer T (iNKT) and germline-encoded mycolyl lipid-reactive (GEMT) [16]. This classification is based on their response speed when encountering new antigens and the ability to form memory cells that persist in long-term immunosurveillance. In this review, we will focus on γδ T cells and their contextual importance in cancer immunosurveillance, and on the reactivation of latent infections such as tuberculosis and virus-infected cells, as these topics require consolidation in the literature but are often neglected in the aging context.First, we will describe γδ T cells and their respective ligands in both mice and human. Next, we will analyze γδ T cells from cradle to grave (i.e., development to old age) to understand their aging trajectory during lifespan. Finally, we will suggest future developments that are necessary for our comprehension of how γδ T cells subsets are affected during the aging process. A better understanding of γδ T cell biology should enable scientists to tailor optimized immunotherapy that targets age-associated immune impairments in th...

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Expansion of human γδ T cells in periphery: Lessons learned from development, infections, and compromised thymic function

Ravens,

Tolosa

2024

Eur J Immunol

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Abstractγδ T cells predominantly develop in the fetal period. Post birth they respond swiftly to environmental insults, pathogens and tumors, especially when other immune effector cells are less ready to function. Most of our understanding of γδ T‐cell development, peripheral adaptation, and function derives from murine studies. The recent advancement of immunological methods allows now to decipher human γδ T‐cell biology in patient cohorts and tissue samples, and to manipulate them using in vitro systems. In this review, we summarize γδ T‐cell development in the human thymus, their functional adaptation to the microbial environment from birth until old age, and their capacity to expand and fill up the peripheral niche under conditions of perturbations of conventional T‐cell development.

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The human fetal thymus generates invariant effector γδ T cells

Cited by 65 publications

References 90 publications

Human γδ TCR Repertoires in Health and Disease

Human γδ TCR Repertoires in Health and Disease

The Aging of γδ T Cells

Expansion of human γδ T cells in periphery: Lessons learned from development, infections, and compromised thymic function

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