T-box 21 transcription factor is responsible for distorted TH2 differentiation in human peripheral CD4+ T cells

Kaminuma, Osamu; Kitamura, Fujiko; Miyatake, Shoichiro; Yamaoka, Kazuko; Miyoshi, Hiroyuki; Inokuma, Shigeko; Tatsumi, Hideki; Nemoto, Soichi; Kitamura, Noriko; Mori, Akio; Hiroi, Takachika

doi:10.1016/j.jaci.2009.01.055

Cited by 25 publications

(39 citation statements)

References 37 publications

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“…3 These TCR-engineered CD4 + cells exhibit antigen-induced cell proliferation, display a multifunctional effector phenotype, and can provide a cognate helper function for generation of MART-1 [27][28][29][30][31][32][33][34][35] CD8 + natural CTL. 12 Since the generation of inflammatory Th1 effectors and type 1 CTL appears to be imperative for the development of effective adoptive immunotherapy, it would be useful to better understand the control of the determination of these phenotypes.…”

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

“…3,12 The antigen-presenting T2 cell line deficient for transporter for antigen presentation (TAP-deficient) was a gift from P. Cresswell, Department of Immunobiology, Yale University. 32 Mart-1 [27][28][29][30][31][32][33][34][35] and MAGE-3 271-279 peptides were purchased from NeoMPS (San Diego, CA). Culture medium consisted of Iscove's modified Dulbecco's medium (IMDM; Invitrogen Life Technologies, Grand Island, NY) supplemented with 10%fetal bovine serum (FBS; Gemini Bioproducts, Calabasas, CA).…”

Section: Study Population Cell Lines Culture Medium and Reagentsmentioning

confidence: 99%

“…Three candidate target sequences (shT-bet2-4) for silencing human T-bet (Gene bank: BC039739.2) were selected by using the shRNA selection tool available at http://sirna.wi.mit.edu/ while the fourth sequence (shT-bet1) was previously described. 34 The T-bet shRNA target sequences (Table 1) were inserted into pLLU2G vector between unique HpaI and XhoI sites and DNA sequencing of inserts and surrounding vector sequences was carried out for confirmation. 35 Lentivector stocks were prepared by transient co-transfection of 293T cells with lentiviral vector plasmid, helper plasmid Δ8.9 expressing pol proteins, a plasmid expressing VSV-G protein and a plasmid expressing Rev protein simultaneously using Lipofectamine 2000 reagent purchased from Invitrogen (Carlsbad, CA) as per the manufacturer's protocol.…”

Section: T-bet Shrna Lentivector Constructionmentioning

confidence: 99%

“…The Mart-1 [27][28][29][30][31][32][33][34][35] epitope-specific retrovector TCR, named DMF5, was obtained from a constitutive GaLV envelope PG13 packaging cell line generously provided by Dr Steven Rosenberg (National Institutes of Health, Bethesda, MD). 12,13,37 Viral supernatants were harvested from subconfluent cells in DMEM with 10% FBS.…”

Section: Mart-1 27-35 Epitope Tcr Retrovectormentioning

confidence: 99%

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Knockdown of T‐bet expression in Mart‐1_27–35‐specific T‐cell‐receptor‐engineered human CD4⁺ CD25⁻ and CD8⁺ T cells attenuates effector function

et al. 2015

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SummaryGene transfer to create tumour epitope-specific cytolytic T cells for adoptive immunotherapy of cancer remains an area of active inquiry. When the Mart-1 27-35 -specific DMF5 T-cell receptor (TCR) is transferred into peripheral human CD4 + T cells, the reprogrammed cells exhibit a T helper type 1 (Th1) phenotype with significant multifactorial effector capabilities. The T-bet transcription factor plays an important role in determination of the Th1 differentiation pathway. To gain a deeper understanding of how T-bet controls the outcome of human T-cell reprogramming by gene transfer, we developed a system for examining the effects of short hairpin RNA-mediated T-bet gene knockdown in sorted cell populations uniformly expressing the knockdown construct. In this system, using activated peripheral human CD4 + CD25 À and CD8 + T cells, T-bet knockdown led to attenuation of the interferon-c response to both antigen-specific and non-specific TCR stimulation. The interleukin-2 (IL-2) antigen-specific response was not attenuated by T-bet knockdown. Also, in TCR-reprogrammed CD8 + cells, the cytolytic effector response was attenuated by T-bet knockdown. T-bet knockdown did not cause redirection into a Th2 differentiation pathway, and no increased IL-4, IL-10, or IL-17 response was detected in this system. These results indicate that T-bet expression is required for maintenance of the CD4 + CD25 À and CD8 + effector phenotypes in TCR-reprogrammed human T cells. They also suggest that the activation protocol necessary for transduction with retrovectors and lentivectors may commit the reprogrammed cells to the Th1 phenotype, which cannot be altered by T-bet knockdown but that there is, nevertheless, a continuous requirement of T-bet expression for interferon-c gene activation.

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Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

Section: Study Population Cell Lines Culture Medium and Reagentsmentioning

confidence: 99%

Section: T-bet Shrna Lentivector Constructionmentioning

confidence: 99%

Section: Mart-1 27-35 Epitope Tcr Retrovectormentioning

confidence: 99%

See 2 more Smart Citations

Knockdown of T‐bet expression in Mart‐1_27–35‐specific T‐cell‐receptor‐engineered human CD4⁺ CD25⁻ and CD8⁺ T cells attenuates effector function

et al. 2015

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“…18B). In concordance with our results, previous studies have also observed increased DNA methylation at the IFN-γ promoter region in naïve CD4+ cells from neonates compared with naïve CD4+ cells from children and adults [224,225,248]. Likewise, Jacoby and colleagues displayed increased methylation at all six CpG sites within the IFN-γ promoter in CBMCs compared to adult PBMCs [249].…”

Section: Age Dependent Changes In Memory and Naïve T Cells (Paper Iii)supporting

confidence: 93%

Immunomodulatory effects of probiotic supplementation during pregnancy and infancy in allergy prevention studies

Forsberg¹

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The Genetics and Epigenetics of Atopic Dermatitis—Filaggrin and Other Polymorphisms

Liang

Chang

2015

Clinic Rev Allerg Immunol

137

108

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Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by a combination of genetic and environmental factors. Genetic evidences depict a complex network comprising by epidermal barrier dysfunctions and dysregulation of innate and adaptive immunity in the pathogenesis of AD. Mutations in the human filaggrin gene (FLG) are the most significant and well-replicated genetic mutation associated with AD, and other mutations associated with epidermal barriers such as SPINK5, FLG-2, SPRR3, and CLDN1 have all been linked to AD. Gene variants may also contribute to the abnormal innate and adaptive responses found in AD, including mutations in PRRs and AMPs, TSLP and TSLPR, IL-1 family cytokines and receptors genes, vitamin D pathway genes, FCER1A, and Th2 and other cytokines genes. GWAS and Immunochip analysis have identified a total of 19 susceptibility loci for AD. Candidate genes at these susceptibility loci identified by GWAS and Immunochip analysis also suggest roles for epidermal barrier functions, innate and adaptive immunity, interleukin-1 family signaling, regulatory T cells, the vitamin D pathway, and the nerve growth factor pathway in the pathogenesis of AD. Increasing evidences show the modern lifestyle (i.e., the hygiene hypothesis, Western diet) and other environmental factors such as pollution and environmental tobacco smoke (ETS) lead to the increasing prevalence of AD with the development of industrialization. Epigenetic alterations in response to these environmental factors, including DNA methylation and microRNA related to immune system and skin barriers, have been found to contribute to the pathogenesis of AD. Genetic variants and epigenetic alteration might be the key tools for the molecular taxonomy of AD and provide the background for the personalized management.

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T-box 21 transcription factor is responsible for distorted TH2 differentiation in human peripheral CD4+ T cells

Cited by 25 publications

References 37 publications

Knockdown of T‐bet expression in Mart‐1_27–35‐specific T‐cell‐receptor‐engineered human CD4⁺ CD25⁻ and CD8⁺ T cells attenuates effector function

Knockdown of T‐bet expression in Mart‐1_27–35‐specific T‐cell‐receptor‐engineered human CD4⁺ CD25⁻ and CD8⁺ T cells attenuates effector function

Immunomodulatory effects of probiotic supplementation during pregnancy and infancy in allergy prevention studies

The Genetics and Epigenetics of Atopic Dermatitis—Filaggrin and Other Polymorphisms

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T-box 21 transcription factor is responsible for distorted TH2 differentiation in human peripheral CD4+ T cells

Cited by 25 publications

References 37 publications

Knockdown of T‐bet expression in Mart‐127–35‐specific T‐cell‐receptor‐engineered human CD4+ CD25− and CD8+ T cells attenuates effector function

Knockdown of T‐bet expression in Mart‐127–35‐specific T‐cell‐receptor‐engineered human CD4+ CD25− and CD8+ T cells attenuates effector function

Immunomodulatory effects of probiotic supplementation during pregnancy and infancy in allergy prevention studies

The Genetics and Epigenetics of Atopic Dermatitis—Filaggrin and Other Polymorphisms

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Product

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Knockdown of T‐bet expression in Mart‐1_27–35‐specific T‐cell‐receptor‐engineered human CD4⁺ CD25⁻ and CD8⁺ T cells attenuates effector function

Knockdown of T‐bet expression in Mart‐1_27–35‐specific T‐cell‐receptor‐engineered human CD4⁺ CD25⁻ and CD8⁺ T cells attenuates effector function