Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4+ Th cells cytotoxic by activating both perforin- and FasL-pathways

Eshima, Koji; Chiba, Sayuri; Suzuki, Harumi; Kokubo, Kenichi; Kobayashi, Hirosuke; Iizuka, Misao; Iwabuchi, Kazuya; Shinohara, Nobukata

doi:10.1016/j.imlet.2012.02.013

Cited by 54 publications

(72 citation statements)

References 57 publications

(67 reference statements)

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“…We found that cytolytic CD4 ϩ T cells represent a distinct subset of CD4 ϩ T cells that differ significantly in their transcriptional and phenotypic profile compared to Th1 cells, characterized by the expression of a module of genes associated with cytolytic function, as well as the T-box transcription factors T-bet and Eomes. Interestingly, the combinational expression of both have been previously shown to be linked to cytolytic function of cytolytic CD4 ϩ T cells in lymphochoriomeningitis virus-infected mice (14), which has also been shown to be linked to the cytolytic activity of CD8 ϩ T cells (29,30). We observed that the transcriptional and phenotypic profile of CD8 ϩ T cells and cytolytic CD4 ϩ T cells were very similar in many respects.…”

Section: Although Cd4supporting

confidence: 56%

“…3A). In contrast, the T-box transcription factor Eomesodermin (EOMES), which has been previously linked to cytolytic functions of CD8 ϩ T cells (14), was significantly higher expressed in cytolytic CD4 ϩ T cells compared to Th1 CD4 ϩ T cells (P Ͻ 0.001). Other transcription factors that have been previously linked to cytolytic activity, including runx3 or THPOK displayed no differences between Th1 and cytolytic CD4 ϩ T cells (data not shown).…”

Section: ) (B) Cd4mentioning

confidence: 95%

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Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

Johnson

Eller

Teigler

et al. 2015

J Virol

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Section: Although Cd4supporting

confidence: 56%

Section: ) (B) Cd4mentioning

confidence: 95%

Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

Johnson

Eller

Teigler

et al. 2015

J Virol

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“…1, B and C). ZNF683 has recently been shown to identify human CD4-CTLs (24), and Eomes and T-bet appear to be important in the development of CD4-CTLs (27, 28). These results confirm that human CD4-CTLs are highly enriched in the T EMRA subset.…”

Section: Resultsmentioning

confidence: 99%

Precursors of human CD4 ⁺ cytotoxic T lymphocytes identified by single-cell transcriptome analysis

et al. 2018

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CD4+ cytotoxic T lymphocytes (CD4-CTLs) have been reported to play a protective role in several viral infections. However, little is known in humans about the biology of CD4-CTL generation, their functional properties, and heterogeneity, especially in relation to other well-described CD4+ memory T cell subsets. We performed single-cell RNA sequencing in more than 9000 cells to unravel CD4-CTL heterogeneity, transcriptional profile, and clonality in humans. Single-cell differential gene expression analysis revealed a spectrum of known transcripts, including several linked to cytotoxic and costimulatory function that are expressed at higher levels in the TEMRA (effector memory T cells expressing CD45RA) subset, which is highly enriched for CD4-CTLs, compared with CD4+ T cells in the central memory (TCM) and effector memory (TEM) subsets. Simultaneous T cell antigen receptor (TCR) analysis in single cells and bulk subsets revealed that CD4-TEMRA cells show marked clonal expansion compared with TCM and TEM cells and that most of CD4-TEMRA were dengue virus (DENV)–specific in donors with previous DENV infection. The profile of CD4-TEMRA was highly heterogeneous across donors, with four distinct clusters identified by the single-cell analysis. We identified distinct clusters of CD4-CTL effector and precursor cells in the TEMRA subset; the precursor cells shared TCR clonotypes with CD4-CTL effectors and were distinguished by high expression of the interleukin-7 receptor. Our identification of a CD4-CTL precursor population may allow further investigation of how CD4-CTLs arise in humans and, thus, could provide insights into the mechanisms that may be used to generate durable and effective CD4-CTL immunity.

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“…Cytotoxic activities of T cells were noticed under controlling of T box transcription factors including T-bet and Eomes through up-regulation of perforin, FasL and granzyme B [63,223]. Eomes interacted with GATA3 to prevent its binding to IL-5 promoter in memory Th2 cells or functioned together with T-bet to mediate generation of IFN-γ producing CD8 + cells [62,76,207].…”

Section: Eomesmentioning

confidence: 99%

Th17 Differentiation and Their Pro-inflammation Function

Song

Gao

Qian

2014

Advances in Experimental Medicine and Biology

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CD4(+) T helper cells are classical but constantly reinterpreted T-cell subset, playing critical roles in a diverse range of inflammatory responses or diseases. Depending on the cytokines they release and the immune responses they mediate, CD4(+) T cells are classically divided into two major cell populations: Th1 and Th2 cells. However, recent studies challenged this Th1/Th2 paradigm by discovering several T-helper cell subsets with specific differentiation program and functions, including Th17 cells, Treg cells, and Tfh cells. In this chapter, we summarize the current understanding and recent progresses on the Th17 lineage differentiation and its effector impacts on variety of inflammatory responses or disease pathogenesis.

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Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4+ Th cells cytotoxic by activating both perforin- and FasL-pathways

Cited by 54 publications

References 57 publications

Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

Precursors of human CD4 ⁺ cytotoxic T lymphocytes identified by single-cell transcriptome analysis

Th17 Differentiation and Their Pro-inflammation Function

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Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4+ Th cells cytotoxic by activating both perforin- and FasL-pathways

Cited by 54 publications

References 57 publications

Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia

Precursors of human CD4 + cytotoxic T lymphocytes identified by single-cell transcriptome analysis

Th17 Differentiation and Their Pro-inflammation Function

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Product

Resources

About

Precursors of human CD4 ⁺ cytotoxic T lymphocytes identified by single-cell transcriptome analysis