TCR stimulation without co-stimulatory signals induces expression of “tolerogenic” genes in memory CD4 T cells but does not compromise cell proliferation

Xie, Anmu; Zheng, Xiangqin; Khattar, Mithun; Schroder, Paul M.; Stepkowski, Stanislaw M.; Xia, Jiahong; Chen, Wenhao

doi:10.1016/j.molimm.2014.09.013

Cited by 2 publications

(3 citation statements)

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“…21 T-cell receptor (TCR) is expressed on mature T cells specifically to recognize non-self-antigens, which are involved in T-cell development, survival, and activation and defend the host from infectious diseases. 22 Stimulation of monoclonal antibodies (mAb) is proved to be more specific than mitogen response in some studies. 23 In many studies on TCR signaling, mAb that recognize the invariant ectodomain of CD3ε have been used to activate T cells.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Interleukin-2 (IL-2) production is a hallmark of activated T cells . T-cell receptor (TCR) is expressed on mature T cells specifically to recognize non-self-antigens, which are involved in T-cell development, survival, and activation and defend the host from infectious diseases . Stimulation of monoclonal antibodies (mAb) is proved to be more specific than mitogen response in some studies .…”

Section: Introductionmentioning

confidence: 99%

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Aflatoxin B₁ Suppressed T-Cell Response to Anti-pig-CD3 Monoclonal Antibody Stimulation in Primary Porcine Splenocytes: A Role for the Extracellular Regulated Protein Kinase (ERK1/2) MAPK Signaling Pathway

Hao

Pan

et al. 2015

J. Agric. Food Chem.

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The aim of the present study is to investigate whether aflatoxin B1 (AFB1)-induced immunotoxicity is associated with oxidative stress and the expression of extracellular regulated protein kinases (ERK) 1/2. The primary splenocytes isolated from healthy pigs were activated and proliferated by anti-pig-CD3 monoclonal antibodies (mAb) in the present experiment, which is an antigen-specific stimulant. Results indicated that cell proliferation and interleukin-2 (IL-2) production were significantly suppressed by AFB1 from 4 to 8 μg/mL in a dose-dependent manner compared to the control group. Furthermore, AFB1 significantly increased malondialdehyde (MDA) levels, decreased reduced glutathione (GSH) and total superoxide dismutase levels, and up-regulated p-ERK1/2 expression in the activated splenocytes. N-Acetyl-l-cysteine blocked anti-CD3-induced T-cell suppression by AFB1 through increasing intracellular concentrations of GSH levels, decreasing MDA levels, and down-regulated p-ERK1/2 expression, respectively. Inhibition of the ERK1/2 expression by ERK-specific iRNA attenuated the decrease of T-cell proliferation and IL-2 production induced by AFB1. It was concluded that AFB1 inhibits anti-CD3-induced lymphocyte proliferation and IL-2 production by the oxidative stress mediated ERK1/2 MAPK signaling pathway.

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Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Aflatoxin B₁ Suppressed T-Cell Response to Anti-pig-CD3 Monoclonal Antibody Stimulation in Primary Porcine Splenocytes: A Role for the Extracellular Regulated Protein Kinase (ERK1/2) MAPK Signaling Pathway

Hao

Pan

et al. 2015

J. Agric. Food Chem.

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“…T cell activation requires the delivery of at least two signals. The first signal is antigen-specific and MHC-TCR ligation, and the second is a co-stimulatory signal [ 13 , 27 , 28 ]. Co-stimulatory signals occur via the binding of CD28, which is located on T cell, with B7 family members on APCs.…”

Section: Discussionmentioning

confidence: 99%

Molecular alterations in the TCR signaling pathway in patients with aplastic anemia

Guo

Zhang

et al. 2016

J Hematol Oncol

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BackgroundA previous study has demonstrated a significantly increased CD3ζ gene expression level in aplastic anemia (AA). However, the mechanism underlying the upregulated CD3ζ mRNA expression level and that of T cell activation signaling molecules in AA patients remains unclear. Thus, we investigated the expression levels of the CD3ζ, CD28, CTLA-4, and Cbl-b genes, the SNP rs231775 in the CTLA-4 gene, and the distribution of the CD3ζ 3′-UTR splice variant in AA patients.MethodsCD3ζ 3′-UTR splice variants were identified in peripheral blood mononuclear cells (PBMCs) from 48 healthy individuals and 67 patients with AA [37 cases of severe aplastic anemia (SAA) and 30 cases of non-sever aplastic anemia (NSAA)] by RT-PCR. CD3ζ, CD28, CTLA-4, and Cbl-b gene expression was analyzed by real-time quantitative PCR. The SNP rs231775 in CTLA-4 gene was analyzed by PCR-RFLP.ResultsCD3ζ and CD28 expression was significantly higher, while CTLA-4 and Cbl-b expression was significantly lower in AA patients compared with healthy individuals. Significantly higher CD3ζ expression was found in the NSAA subgroup compared with the SAA subgroup. 64 % of the AA samples had the same genotype (WT+AS+CD3ζ 3′-UTR); 22 % of the AA patients had a WT+AS−CD3ζ 3′-UTR genotype, and 14 % of the AA patients had a WT−AS+CD3ζ 3′-UTR genotype. The CD3ζ expression level of WT−AS+ subgroup was the highest in the SAA patients. A significantly higher frequency of the GG genotype (mutant type, homozygous) of SNP rs231775 in CTLA-4 gene was found in the AA patients. Positive correlation between the CTLA-4 and Cbl-b gene expression levels was found in healthy individuals with the AA and AG genotypes, but not in the AA patients.ConclusionsThis is the first study analyzing the expression characteristics of the CD28, CTLA-4, and Cbl-b genes in AA. Our results suggest that aberrant T cell activation may be related to the first and second signals of T cell activation in AA. The GG genotype of SNP rs231775 in CTLA-4 gene might be associated with AA risk in the Chinese population. The characteristics of CD3ζ 3′-UTR alternative splicing may be an index for evaluating the T cell activation status in AA patients, particularly in SAA patients.

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TCR stimulation without co-stimulatory signals induces expression of “tolerogenic” genes in memory CD4 T cells but does not compromise cell proliferation

Cited by 2 publications

References 38 publications

Aflatoxin B₁ Suppressed T-Cell Response to Anti-pig-CD3 Monoclonal Antibody Stimulation in Primary Porcine Splenocytes: A Role for the Extracellular Regulated Protein Kinase (ERK1/2) MAPK Signaling Pathway

Aflatoxin B₁ Suppressed T-Cell Response to Anti-pig-CD3 Monoclonal Antibody Stimulation in Primary Porcine Splenocytes: A Role for the Extracellular Regulated Protein Kinase (ERK1/2) MAPK Signaling Pathway

Molecular alterations in the TCR signaling pathway in patients with aplastic anemia

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TCR stimulation without co-stimulatory signals induces expression of “tolerogenic” genes in memory CD4 T cells but does not compromise cell proliferation

Cited by 2 publications

References 38 publications

Aflatoxin B1 Suppressed T-Cell Response to Anti-pig-CD3 Monoclonal Antibody Stimulation in Primary Porcine Splenocytes: A Role for the Extracellular Regulated Protein Kinase (ERK1/2) MAPK Signaling Pathway

Aflatoxin B1 Suppressed T-Cell Response to Anti-pig-CD3 Monoclonal Antibody Stimulation in Primary Porcine Splenocytes: A Role for the Extracellular Regulated Protein Kinase (ERK1/2) MAPK Signaling Pathway

Molecular alterations in the TCR signaling pathway in patients with aplastic anemia

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Aflatoxin B₁ Suppressed T-Cell Response to Anti-pig-CD3 Monoclonal Antibody Stimulation in Primary Porcine Splenocytes: A Role for the Extracellular Regulated Protein Kinase (ERK1/2) MAPK Signaling Pathway

Aflatoxin B₁ Suppressed T-Cell Response to Anti-pig-CD3 Monoclonal Antibody Stimulation in Primary Porcine Splenocytes: A Role for the Extracellular Regulated Protein Kinase (ERK1/2) MAPK Signaling Pathway