scholarly journals Interleukin‐25 initiates Th2 differentiation of human CD4 + T cells and influences expression of its own receptor

2015 ◽  
Vol 3 (4) ◽  
pp. 455-468 ◽  
Author(s):  
Graeme Bredo ◽  
Jessica Storie ◽  
Nami Shrestha Palikhe ◽  
Courtney Davidson ◽  
Alexis Adams ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Interleukin 25 ◽  
Th2 Differentiation

scholarly journals TSLP and IL-7 use two different mechanisms to regulate human CD4+ T cell homeostasis

2009 ◽  
Vol 206 (10) ◽  
pp. 2111-2119 ◽  
Author(s):  
Ning Lu ◽  
Yi-Hong Wang ◽  
Yui-Hsi Wang ◽  
Kazuhiko Arima ◽  
Shino Hanabuchi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Th2 Cells ◽  
T Cell Proliferation ◽  
T Cell Homeostasis ◽  
Cell Homeostasis ◽  
Th2 Differentiation

Whether thymic stromal lymphopoietin (TSLP) directly induces potent human CD4+ T cell proliferation and Th2 differentiation is unknown. We report that resting and activated CD4+ T cells expressed high levels of IL-7 receptor a chain but very low levels of TSLP receptor (TSLPR) when compared with levels expressed in myeloid dendritic cells (mDCs). This was confirmed by immunohistology and flow cytometry analyses showing that only a subset of mDCs, with more activated phenotypes, expressed TSLPR in human tonsils in vivo. IL-7 induced strong STAT1, -3, and -5 activation and promoted the proliferation of naive CD4+ T cells in the presence of anti-CD3 and anti-CD28 monoclonal antibodies, whereas TSLP induced weak STAT5 activation, associated with marginally improved cell survival and proliferation, but failed to induce cell expansion and Th2 differentiation. The effect of TSLP on enhancing strong human T cell proliferation was observed only when sorted naive CD4+ T cells were cultured with mDCs at levels as low as 0.5%. TSLP could only induce naive CD4+ T cells to differentiate into Th2 cells in the presence of allogeneic mDCs. These results demonstrate that IL-7 and TSLP use different mechanisms to regulate human CD4+ T cell homeostasis.

scholarly journals Exogenous Hydrogen Peroxide Induces Lipid Raft-Mediated STAT-6 Activation in T Cells

2017 ◽  
Vol 42 (6) ◽  
pp. 2467-2480 ◽  
Author(s):  
Hee Ja Kim ◽  
Jiwoo Lim ◽  
Young-Soon Jang ◽  
Eui-Cheol Shin ◽  
Hyung-Ran Kim ◽  
...  
Keyword(s):  
T Cells ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Cd4 T Cells ◽  
Adaptive Immune Response ◽  
T Cell Subsets ◽  
H2o2 Treatment ◽  
Gel Shift Assay ◽  
Initiating Factors ◽  
Th2 Differentiation

Background/Aims: CD4+ T cells are a critical component of the adaptive immune response. While the mechanisms controlling the differentiation of the Th1, Th17, and regulatory T cell subsets from naïve CD4+ T cells are well described, the factors that induce Th2 differentiation are still largely unknown. Methods: The effects of treatment with exogenous H2O2 on STAT-6 phosphorylation and activation in T cells were examined by immunoblotting, immunofluorescence and gel shift assay. Anti-CD3 antibody and methyl-β-cyclodextrin were utilized to induce lipid raft assembly and to investigate the involvement of lipid rafts, respectively. Results: Jurkat and EL-4 T cells that were exposed to H2O2 showed rapid and strong STAT-6 phosphorylation, and the extent of STAT-6 phosphorylation was enhanced by co-treatment with anti-CD3 antibody. The effect of H2O2 on STAT-6 phosphorylation and translocation was inhibited by disruption of lipid rafts. STAT-6 activation in response to H2O2 treatment regulated IL-4 gene expression, and this response was strengthened by treatment with anti-CD3. Conclusion: Our results indicate that reactive oxygen species such as H2O2 can act on upstream and initiating factors for activation of STAT-6 in T cells and contribute to formation of a positive feedback loop between STAT-6 and IL-4 in the Th2 differentiation process.

scholarly journals Alloantibody Production is Regulated by CD4+ T Cells' Alloreactive Pathway, Rather Than Precursor Frequency or Th1/Th2 Differentiation

2004 ◽  
Vol 4 (8) ◽  
pp. 1237-1245 ◽  
Author(s):  
Dominike Sauve ◽  
Myriam Baratin ◽  
Caroline Leduc ◽  
Karina Bonin ◽  
Claude Daniel
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Precursor Frequency ◽  
Th2 Differentiation

scholarly journals A role for TSLP in the development of inflammation in an asthma model

2005 ◽  
Vol 202 (6) ◽  
pp. 829-839 ◽  
Author(s):  
Amin Al-Shami ◽  
Rosanne Spolski ◽  
John Kelly ◽  
Andrea Keane-Myers ◽  
Warren J. Leonard
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Interferon Γ ◽  
Cd4 T Cell ◽  
T Cell Homeostasis ◽  
Asthma Model ◽  
Memory Cd4 T Cells ◽  
Th2 Differentiation

Thymic stromal lymphopoietin (TSLP) is a cytokine that promotes CD4+ T cell homeostasis. We now demonstrate that TSLP is required to mount a normal CD4+ T cell–mediated inflammatory response. TSLP acts directly on naive, but not, memory CD4+ T cells, and promotes their proliferation in response to antigen. In addition, TSLP exerts an effect indirectly through DCs to promote Th2 differentiation of CD4+ T cells. Correspondingly, TSLP receptor (TSLPR) knockout (KO) mice exhibit strong Th1 responses, with high levels of interleukin (IL)-12, interferon-γ, and immunoglobulin (Ig) G2a, but low production of IL-4, -5, -10, -13, and IgE; moreover, CD4+ T cells from these animals proliferate less well in response to antigen. Furthermore, TSLPR KO mice fail to develop an inflammatory lung response to inhaled antigen unless supplemented with wild-type CD4+ T cells. This underscores an important role for this cytokine in the development of inflammatory and/or allergic responses in vivo.

CD4+ T Cells From Nasal Polyp Explants Contain Abundant Th2 Cells Expressing Functional Interleukin-25 Receptors Together With Th17 Cells

2014 ◽  
Vol 133 (2) ◽  
pp. AB87
Author(s):  
Emily Lam ◽  
Harsha H. Kariyawasam ◽  
Stephen R. Durham ◽  
Joanne Rimmer ◽  
Valerie J. Lund ◽  
...  
Keyword(s):  
T Cells ◽  
Nasal Polyp ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Th2 Cells ◽  
Interleukin 25

scholarly journals The Runx1 Transcription Factor Inhibits the Differentiation of Naive CD4+ T Cells into the Th2 Lineage by Repressing GATA3 Expression

2003 ◽  
Vol 198 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Okiru Komine ◽  
Keitaro Hayashi ◽  
Waka Natsume ◽  
Toshio Watanabe ◽  
Youichi Seki ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Cell Differentiation ◽  
Cd4 T Cells ◽  
Negative Regulator ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Endogenous Expression ◽  
Gata3 Expression ◽  
Th2 Differentiation

Differentiation of naive CD4+ T cells into helper T (Th) cells is controlled by a combination of several transcriptional factors. In this study, we examined the functional role of the Runx1 transcription factor in Th cell differentiation. Naive T cells from transgenic mice expressing a dominant interfering form of Runx1 exhibited enhanced interleukin 4 production and efficient Th2 differentiation. In contrast, transduction of Runx1 into wild-type T cells caused a complete attenuation of Th2 differentiation and was accompanied by the cessation of GATA3 expression. Furthermore, endogenous expression of Runx1 in naive T cells declined after T cell receptor stimulation, at the same time that expression of GATA3 increased. We conclude that Runx1 plays a novel role as a negative regulator of GATA3 expression, thereby inhibiting the Th2 cell differentiation.

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

2009 ◽  
Vol 123 (4) ◽  
pp. 813-823.e3 ◽  
Author(s):  
Osamu Kaminuma ◽  
Fujiko Kitamura ◽  
Shoichiro Miyatake ◽  
Kazuko Yamaoka ◽  
Hiroyuki Miyoshi ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Cd4 T Cells ◽  
T Box ◽  
Th2 Differentiation

Alpha-Synuclein Deficiency Is Associated with Defective Th2 Differentiation and Enhanced Regulatory T Cell Development

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1424-1424
Author(s):  
Afshin Shameli ◽  
Yan Zheng ◽  
Clifford Harding ◽  
Howard Meyerson ◽  
Robert Maitta
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Alpha Synuclein ◽  
Activation Markers ◽  
Lineage Differentiation ◽  
And Function ◽  
Th2 Differentiation ◽  
B And T Lymphocytes

Abstract Synucleins (including α-, β- and γ-synucleins) are a group of proteins that are highly expressed in the central nervous system. Alpha-synuclein, in particular, has been implicated in the pathogenesis of neurodegenerative disorders known as synucleinopathies. The function of these proteins in other organ systems is largely unknown. Some studies have demonstrated expression of α-synuclein on peripheral blood mononuclear cells (PBMC), including B and T lymphocytes, NK cells and monocytes; and its expression has been shown to be higher in PBMCs of individuals with Parkinson’s compared to healthy controls. We have recently shown that α-synuclein-deficiency is associated with marked defect in development of mature B and T lymphocytes. In particular, we showed enhanced negative selection of developing thymic T cells in the absence α-synuclein. Furthermore, we demonstrated that α-synuclein-deficiency is associated with an impaired IgG response to T cell-dependent antigens. Here we used age and sex-matched α-synuclein knock-out (KO) and wild type (WT) mice to further investigate the lineage differentiation and activation of T cells. We found that few splenic T cells that develop in KO mice contain a higher percentage of CD8+ T cell expressing early activation markers CD69 (7.6 ± 0.09 for KO vs. 5.3 ± 0.23 for WT, p=0.005, figure 1A) and CD49d (12.97 ± 0.3 for KO vs. 7.32 ± 0.6 for WT, p=0.006, figure 1A). A similar trend was noted for CD4+ CD49d+ T cells, although the difference did not reach statistical significance (23.90 ± 3.48 for KO vs.13.23 ± 0.73 for WT, p=0.086, figure 1A). No difference was noted in the expression of late activation marker CD44, and lymph node homing marker CD62L. This was associated with significantly increased IL-2 production from KO CD4+ T cells (OD 2.70 ± 0.12 for KO vs.1.05 ± 0.39 for WT, p=0.002, figure 1B) and a trend for increased IFN-γ production from KO CD4+ T cells (OD 2.89 ± 0.33 for KO vs.2.12 ± 0.59 for WT, p=0.12) after in vitro activation with anti-CD3/anti-CD28 beads. Interestingly, In vitro activation of splenic CD4+ T cells resulted in significantly reduced IL-4 production from KO T cells (OD 0.20 ± 0.14 for KO, vs. 0.74 ± 0.31 for WT, p=0.05, Figure 2) suggesting a defective Th2 differentiation in KO CD4+ T cells. Further flow cytometric analysis of T cells showed that while thymic Foxp3+ CD4+ regulatory T cells are significantly reduced in KO mice (3.07 ±0.35 for KO vs. 5.00 ± 0.87 for WT, p=0.02, Figure 3), the percentage of splenic Foxp3+ CD4+ T cells is higher in the KO mice compared to WT mice (18.33 ± 4.90 for KO vs.10.33 ± 1.39 for WT, p=0.05, Figure 3). No difference was noted among NK cells from KO and WT mice. In summary, we demonstrate a role for α-synuclein in lineage differentiation and function of T cells. While α-synuclein-deficiency leads to a significant defect in development of mature T cells, the small population of cells that do mature, express higher levels of early activation markers, and produce higher levels of IL-2 upon antigenic stimulation. Of interest, these cells are defective in IL-4 production. Additionally, we also show that α-synuclein-deficiency is associated with a higher percentage of peripheral CD4+ Foxp3+ T cells, a finding that might be explained by higher levels of IL-2 production by α-synuclein-deficient CD4+ T cells, although a direct effect of α-synuclein on the survival of regulatory T cells cannot be excluded. The underlying mechanism for the function α-synuclein in development and function of T cells is subject of future studies. Disclosures No relevant conflicts of interest to declare.

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