The CD4-centered universe of human T cell subsets

Geginat, Jens; Paroni, Moira; Facciotti, Federica; Gruarin, Paola; Kastirr, Ilko; Caprioli, Flavio; Pagani, Massimiliano; Abrignani, Sergio

doi:10.1016/j.smim.2013.10.012

Cited by 91 publications

(103 citation statements)

References 234 publications

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“…CD4+ T cells are typically categorized by the level of expression of surface and intracellular proteins that reflect functionally distinct cell types [11,12]. However, T cells are highly heterogeneous, displaying diverse combinations of surface markers and effector functions.…”

Section: Introductionmentioning

confidence: 99%

Leveraging blood and tissue CD4+ T cell heterogeneity at the single cell level to identify mechanisms of disease in rheumatoid arthritis

Fonseka

Rao

Raychaudhuri

2017

Current Opinion in Immunology

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CD4+ T cells have been long known to play an important role in the pathogenesis of rheumatoid arthritis (RA), but the specific cell populations and states that drive the disease have been challenging to identify with low dimensional single cell data and bulk assays. The advent of high dimensional single cell technologies – like single cell RNA-seq or mass cytometry – has offered promise to defining key populations, but brings new methodological and statistical challenges. Recent single cell profiling studies have revealed a broad diversity of cell types among CD4+ T cells, identifying novel populations that are expanded or altered in RA. Here we will review recent findings on CD4+ T cell heterogeneity and RA that have come from single cell profiling studies and discuss the best practices for conducting these studies.

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Section: Introductionmentioning

confidence: 99%

Leveraging blood and tissue CD4+ T cell heterogeneity at the single cell level to identify mechanisms of disease in rheumatoid arthritis

Fonseka

Rao

Raychaudhuri

2017

Current Opinion in Immunology

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“…Recently, a subset of CD8 + T SCM with high expansion potential and low effector functions was identified, which can be discriminated from naive T cells by CD95 expression (24). We found that CD4 + T SCM were present at variable frequencies in conventional naive T cell preparations, and that relevant fractions expressed CCR6 or CD161, indicating that they were committed to the Th17 lineage (7,15,32). Consistently, these cells produced IL-17 and IL-22 ex vivo and further upregulated cytokine production upon in vitro expansion in the absence of polarizing cytokines.…”

Section: Discussionmentioning

confidence: 83%

Signal Strength and Metabolic Requirements Control Cytokine-Induced Th17 Differentiation of Uncommitted Human T Cells

Kastirr

Crosti

Maglie

et al. 2015

The Journal of Immunology

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IL-17 production defines Th17 cells, which orchestrate immune responses and autoimmune diseases. Human Th17 cells can be efficiently generated with appropriate cytokines from precommitted precursors, but the requirements of uncommitted T cells are still ill defined. In standard human Th17 cultures, IL-17 production was restricted to CCR6+CD45RA+ T cells, which expressed CD95 and produced IL-17 ex vivo, identifying them as Th17 memory stem cells. Uncommitted naive CD4+ T cells upregulated CCR6, RORC2, and IL-23R expression with Th17-promoting cytokines but in addition required sustained TCR stimulation, late mammalian target of rapamycin (mTOR) activity, and HIF-1α to produce IL-17. However, in standard high-density cultures, nutrients like glucose and amino acids became progressively limiting, and mTOR activity was consequently not sustained, despite ongoing TCR stimulation and T cell proliferation. Sustained, nutrient-dependent mTOR activity also induced spontaneous IL-22 and IFN-γ production, but these cytokines had also unique metabolic requirements. Thus, glucose promoted IL-12–independent Th1 differentiation, whereas aromatic amino acid–derived AHR ligands were selectively required for IL-22 production. The identification of Th17 memory stem cells and the stimulation requirements for induced human Th17/22 differentiation have important implications for T cell biology and for therapies targeting the mTOR pathway.

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“…These T helper (Th) subsets are characterized by a unique pattern of cytokine expression, which is controlled by specific master transcription factors [42] (Fig. 4a).…”

Section: T Cell Mediated Immune Responsesmentioning

confidence: 99%

“…At this stage, differentiated Th cells also acquire chemokine receptors that allow Th cells to leave the LN and migrate to the site of the infection. Once effector T cells migrate to the site of infection and encounter a cell expressing a cognate pMHC molecule they secrete the appropriate cytokines to enable the destruction of the pathogen [42]. For example, in the case of an infection with an intracellular pathogen Th1 cells secrete IFN-γ, which activates tissue macrophages to produce reactive oxygen and nitrogen species and increases MHC and costimulatory molecule expression levels leading to more efficient killing and antigen presentation by macrophages.…”

Section: T Cell Mediated Immune Responsesmentioning

confidence: 99%

An immunology primer for computational modelers

Hawse

Morel

2014

J Pharmacokinet Pharmacodyn

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The immune system is designed to protect an organism from infection and damage caused by a pathogen. A successful immune response requires the coordinated function of multiple cell types and molecules in the innate and adaptive immune systems. Given the complexity of the immune system, it would be advantageous to build computational models to better understand immune responses and develop models to better guide the design of immunotherapies. Often, researchers with strong quantitative backgrounds do not have formal training in immunology. Therefore, the goal of this review article is to provide a brief primer on cellular immunology that is geared for computational modelers.

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The CD4-centered universe of human T cell subsets

Cited by 91 publications

References 234 publications

Leveraging blood and tissue CD4+ T cell heterogeneity at the single cell level to identify mechanisms of disease in rheumatoid arthritis

Leveraging blood and tissue CD4+ T cell heterogeneity at the single cell level to identify mechanisms of disease in rheumatoid arthritis

Signal Strength and Metabolic Requirements Control Cytokine-Induced Th17 Differentiation of Uncommitted Human T Cells

An immunology primer for computational modelers

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