Five Layers of Receptor Signaling in Î³Î´ T-Cell Differentiation and Activation

Ribeiro, Sérgio T.; Ribot, Julie C.; Silva‐Santos, Bruno

doi:10.3389/fimmu.2015.00015

Cited by 101 publications

(101 citation statements)

References 125 publications

(119 reference statements)

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“…Since the discovery of γδ T cells in the mid-1980s in humans, these cells have been considered as an enigmatic population that exhibits the characteristics of both innate and adaptive immune functions, such as participating in rapid resistance to pathogen infections, acting as an APC to initiate adaptive immunity, and performing CD4 + Th and CD8 + CTL-like functions (4, 30). Thus, the γδ T cells are thought to be a more primordial lymphocyte subset with a long evolutionary history throughout vertebrate evolution (31).…”

Section: Discussionmentioning

confidence: 99%

Characterization of γδ T Cells from Zebrafish Provides Insights into Their Important Role in Adaptive Humoral Immunity

Wan

et al. 2017

Front. Immunol.

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γδ T cells represent an evolutionarily primitive T cell subset characterized by distinct T cell receptors (TCRs) and innate and adaptive immune functions. However, the presence of this T cell subset in ancient vertebrates remains unclear. In this study, γδ T cells from a zebrafish (Danio rerio) model were subjected to molecular and cellular characterizations. The constant regions of zebrafish TCR-γ (DrTRGC) and δ (DrTRDC) were initially identified. Zebrafish γδ T cells accounted for 7.7–20.5% of the total lymphocytes in spleen, head kidney, peripheral blood, skin, gill, and intestine tissues. They possess typical morphological features of lymphocytes with a surface phenotype of γ+δ+CD4−CD8+. Zebrafish γδ T cells functionally showed a potent phagocytic ability to both soluble and particulate antigens. They can also act as an antigen-presenting cell to initiate antigen (KLH)-specific CD4+ TKLH cell activation and to induce B cell proliferation and IgM production. Particularly, zebrafish γδ T cells also play a critical role in antigen-specific IgZ production in intestinal mucus. These findings demonstrated that γδ T cells had been originated as early as teleost fish, which providing valuable insights into the evolutionary history of T cell subset. It is anticipated that this study would be used as a guide to develop a zebrafish model for the cross-species investigation of γδ T cell biology.

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Section: Discussionmentioning

confidence: 99%

Characterization of γδ T Cells from Zebrafish Provides Insights into Their Important Role in Adaptive Humoral Immunity

Wan

et al. 2017

Front. Immunol.

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“…γδT cells can rapidly respond to a variety of protein‐ and non‐protein‐based antigens. γδT cells express pattern recognition receptors (PRRs), including Toll‐like receptors (TLRs) and C‐type lectin receptors . Equipped with these sensors that can recognize DAMPs and pathogen‐associated molecular patterns, the role of γδT cells in inflammatory responses has been increasingly appreciated.…”

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confidence: 99%

γδ T Cells Promote Steatohepatitis by Orchestrating Innate and Adaptive Immune Programming

Torres‐Hernandez

Wang

Nikiforov³

et al. 2019

Hepatology

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Background and Aims The recruitment and activation of inflammatory cells in the liver delineates the transition from hepatic steatosis to steatohepatitis (SH). Approach and Results We found that in SH, γδT cells are recruited to the liver by C‐C chemokine receptor (CCR) 2, CCR5, and nucleotide‐binding oligomerization domain‐containing protein 2 signaling and are skewed toward an interleukin (IL)‐17A+ phenotype in an inducible costimulator (ICOS)/ICOS ligand–dependent manner. γδT cells exhibit a distinct Vγ4+, PD1+, Ly6C+CD44+ phenotype in SH. Moreover, γδT cells up‐regulate both CD1d, which is necessary for lipid‐based antigens presentation, and the free fatty acid receptor, CD36. γδT cells are stimulated to express IL‐17A by palmitic acid and CD1d ligation. Deletion, depletion, and targeted interruption of γδT cell recruitment protects against diet‐induced SH and accelerates disease resolution. Conclusions We demonstrate that hepatic γδT cells exacerbate SH, independent of IL‐17 expression, by mitigating conventional CD4+ T‐cell expansion and modulating their inflammatory program by CD1d‐dependent vascular endothelial growth factor expression.

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“…Cytokines and chemokines are soluble factors that are secreted by cells to communicate among themselves, contributing to downstream effects such as activation, proliferation and recruitment, which are essential to resolving an infection. Studies have shown that γδ T cell subsets are able to respond to IL-12, IL-15, IL-18 which then leads to activation, the secretion of cytokines and proliferation [139]. In aging studies on αβ T cells, the authors have shown that elderly T cells display attenuated tyrosine phosphorylation of the protein tyrosine kinase ZAP-70, LAT and PLCγ due to TNFα and reduced phosphorylation of STAT3 and STAT5; this is possibly due to the increased expression of suppressor of cytokine signaling 3 (SOCS3) caused by IL-6.…”

Section: Cytokines Chemokines and γδ T Cellsmentioning

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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Five Layers of Receptor Signaling in Î³Î´ T-Cell Differentiation and Activation

Cited by 101 publications

References 125 publications

Characterization of γδ T Cells from Zebrafish Provides Insights into Their Important Role in Adaptive Humoral Immunity

Characterization of γδ T Cells from Zebrafish Provides Insights into Their Important Role in Adaptive Humoral Immunity

γδ T Cells Promote Steatohepatitis by Orchestrating Innate and Adaptive Immune Programming

The Aging of γδ T Cells

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