scholarly journals Induction of Th2 cell differentiation in the primary immune response: dendritic cells isolated from adherent cell culture treated with IL-10 prime naive CD4+ T cells to secrete IL-4

1998 ◽  
Vol 10 (8) ◽  
pp. 1017-1026 ◽  
Author(s):  
L Liu
Keyword(s):  
Cell Culture ◽  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Cell Differentiation ◽  
Cd4 T Cells ◽  
Primary Immune Response ◽  
Adherent Cell ◽  
Th2 Cell ◽  
Adherent Cell Culture

scholarly journals Differentiation and stability of T helper 1 and 2 cells derived from naive human neonatal CD4+ T cells, analyzed at the single-cell level.

1996 ◽  
Vol 184 (2) ◽  
pp. 473-483 ◽  
Author(s):  
T Sornasse ◽  
P V Larenas ◽  
K A Davis ◽  
J E de Vries ◽  
H Yssel
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Cd4 T Cells ◽  
Biological Activities ◽  
Th2 Cells ◽  
Cell Phenotype ◽  
T Helper ◽  
Th1 Cell ◽  
Th2 Cell ◽  
Th1 And Th2

The development of CD4+ T helper (Th) type 1 and 2 cells is essential for the eradication of pathogens, but can also be responsible for various pathological disorders. Therefore, modulation of Th cell differentiation may have clinical utility in the treatment of human disease. Here, we show that interleukin (IL) 12 and IL-4 directly induce human neonatal CD4- T cells, activated via CD3 and CD28, to differentiate into Th1 and Th2 subsets. In contrast, IL-13, which shares many biological activities with IL-4, failed to induce T cell differentiation, consistent with the observation that human T cells do not express IL-13 receptors. Both the IL-12-induced Th1 subset and the IL-4-induced Th2 subset produce large quantities of IL-10, confirming that human IL-10 is not a typical human Th2 cytokine. Interestingly, IL-4-driven Th2 cell differentiation was completely prevented by an IL-4 mutant protein (IL-4.Y124D), indicating that this molecule acts as a strong IL-4 receptor antagonist. Analysis of single T cells producing interferon gamma or IL-4 revealed that induction of Th1 cell differentiation occurred rapidly and required only 4 d of priming of the neonatal CD4+ T cells in the presence of IL-12. The IL-12-induced Th1 cell phenotype was stable and was not significantly affected when repeatedly stimulated in the presence of recombinant IL-4. In contrast, the differentiation of Th2 cells occurred slowly and required not only 6 d of priming, but also additional restimulation of the primed CD4+ T cells in the presence of IL-4. Moreover, IL-4-induced Th2 cell phenotypes were not stable and could rapidly be reverted into a population predominantly containing Th0 and Th1 cells, after a single restimulation in the presence of IL-12. The observed differences in stability of IL-12- and IL-4-induced human Th1 and Th2 subsets, respectively, may have implications for cytokine-based therapies of chronic disease.

scholarly journals Downregulation of miRNA-451a Promotes the Differentiation of CD4+ T Cells towards Th2 Cells by Upregulating ETS1 in Childhood Asthma

2020 ◽  
pp. 1-11
Author(s):  
Tianyue  Wang ◽  
Qianlan Zhou ◽  
Yunxiao Shang
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Cd4 T Cells ◽  
Peripheral Blood Lymphocytes ◽  
Cell Polarization ◽  
Luciferase Assay ◽  
Th2 Cells ◽  
Th2 Cell ◽  
Novel Target

Children exposed to common aeroallergens may develop asthma that progresses into adulthood. Inflammation regulated by T helper 2 (Th2) cells, a specific subpopulation of CD4+ T lymphocytes, is involved in asthmatic injury. Herein, our microarray data indicated that microRNA-451a-5p (miRNA-451a) expression decreased by 4.6-fold and ETS proto-oncogene 1 (ETS1) increased by 2.2-fold in the peripheral blood lymphocytes isolated from asthmatic children (<i>n</i> = 4) as compared to control individuals (<i>n</i> = 4). The negative correlation between miRNA-451a and ETS1 was further validated in 40 CD4+ T cell samples (10 healthy vs. 30 asthmatic samples). In vitro, naïve CD4+ T cells isolated from control individuals were cultured under Th2 cell polarizing condition. miRNA-451a expression decreased while ETS1 increased in CD4+ T cells in the setting of Th2 cell polarization. Moreover, miRNA-451a knockdown enhanced Th2 cell polarization – cells positive for both GATA3 (GATA binding protein 3, a Th2-transcription factor) and CD4 increased, and the generation of Th2 cell cytokines, interleukin (IL)5 and IL13, increased. In contrast, miRNA-451a overexpression inhibited Th2 cell differentiation. Interestingly, dual-Luciferase assay proved ETS1 as a novel target of miRNA-451a. Moreover, enforced expression of ETS1 partially restored miRNA-451a-induced inhibition of IL5 and IL13, and increased the GATA3+CD4+ cell population. Collectively, our work demonstrates that downregulation of miRNA-451a upregulates ETS1 expression in CD4+ T cells, which may contribute to Th2 cell differentiation in pediatric asthma.

Azithromycin modulates immune response of human monocyte-derived dendritic cells and CD4 + T cells

2016 ◽  
Vol 40 ◽  
pp. 318-326 ◽  
Author(s):  
Syh-Jae Lin ◽  
Ming-Ling Kuo ◽  
Hsiu-Shan Hsiao ◽  
Pei-Tzu Lee
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Cd4 T Cells ◽  
Human Monocyte

scholarly journals Responsiveness of Naive CD4 T Cells to Polarizing Cytokine Determines the Ratio of Th1 and Th2 Cell Differentiation

2006 ◽  
Vol 176 (3) ◽  
pp. 1553-1560 ◽  
Author(s):  
Natallia Mikhalkevich ◽  
Brian Becknell ◽  
Michael A. Caligiuri ◽  
Michael D. Bates ◽  
Richard Harvey ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
Cd4 T Cells ◽  
Th2 Cell ◽  
Th1 And Th2

scholarly journals Down-regulation of Gfi-1 expression by TGF-β is important for differentiation of Th17 and CD103+ inducible regulatory T cells

2009 ◽  
Vol 206 (2) ◽  
pp. 329-341 ◽  
Author(s):  
Jinfang Zhu ◽  
Todd S. Davidson ◽  
Gang Wei ◽  
Dragana Jankovic ◽  
Kairong Cui ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Growth Factor ◽  
Cd4 T Cells ◽  
Cell Expansion ◽  
Conditional Knockout ◽  
Th2 Cells ◽  
Th2 Cell ◽  
Itreg Cell

Growth factor independent 1 (Gfi-1), a transcriptional repressor, is transiently induced during T cell activation. Interleukin (IL) 4 further induces Gfi-1, resulting in optimal Th2 cell expansion. We report a second important function of Gfi-1 in CD4 T cells: prevention of alternative differentiation by Th2 cells, and inhibition of differentiation of naive CD4 T cells to either Th17 or inducible regulatory T (iTreg) cells. In Gfi1−/− Th2 cells, the Rorc, Il23r, and Cd103 loci showed histone 3 lysine 4 trimethylation modifications that were lacking in wild-type Th2 cells, implying that Gfi-1 is critical for epigenetic regulation of Th17 and iTreg cell–related genes in Th2 cells. Enforced Gfi-1 expression inhibited IL-17 production and iTreg cell differentiation. Furthermore, a key inducer of both Th17 and iTreg cell differentiation, transforming growth factor β, repressed Gfi-1 expression, implying a reciprocal negative regulation of CD4 T cell fate determination. Chromatin immunoprecipitation showed direct binding of the Gfi-1–lysine-specific demethylase 1 repressive complex to the intergenic region of Il17a/Il17f loci and to intron 1 of Cd103. T cell–specific Gfi1 conditional knockout mice displayed a striking delay in the onset of experimental allergic encephalitis correlated with a dramatic increase of Foxp3+CD103+ CD4 T cells. Thus, Gfi-1 plays a critical role both in enhancing Th2 cell expansion and in repressing induction of Th17 and CD103+ iTreg cells.

scholarly journals GATA-3 in Human T Cell Helper Type 2 Development

2004 ◽  
Vol 199 (3) ◽  
pp. 423-428 ◽  
Author(s):  
Alla Skapenko ◽  
Jan Leipe ◽  
Uwe Niesner ◽  
Koen Devriendt ◽  
Rolf Beetz ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Differentiation ◽  
Mrna Levels ◽  
Effector Functions ◽  
Th2 Cell ◽  
Human T Cell

The delineation of the in vivo role of GATA-3 in human T cell differentiation is a critical step in the understanding of molecular mechanisms directing human immune responses. We examined T cell differentiation and T cell–mediated effector functions in individuals lacking one functional GATA-3 allele. CD4 T cells from GATA-3+/− individuals expressed significantly reduced levels of GATA-3, associated with markedly decreased T helper cell (Th)2 frequencies in vivo and in vitro. Moreover, Th2 cell–mediated effector functions, as assessed by serum levels of Th2-dependent immunoglobulins (Igs; IgG4, IgE), were dramatically decreased, whereas the Th1-dependent IgG1 was elevated compared with GATA-3+/+ controls. Concordant with these data, silencing of GATA-3 in GATA-3+/+ CD4 T cells with small interfering RNA significantly reduced Th2 cell differentiation. Moreover, GATA-3 mRNA levels increased under Th2-inducing conditions and decreased under Th1-inducing conditions. Taken together, the data strongly suggest that GATA-3 is an important transcription factor in regulating human Th2 cell differentiation in vivo.

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