Prostaglandin I2analogs inhibit Th1 and Th2 effector cytokine production by CD4 T cells

2006 ◽  
Vol 81 (3) ◽  
pp. 809-817 ◽  
Author(s):  
Weisong Zhou ◽  
Timothy S. Blackwell ◽  
Kasia Goleniewska ◽  
Jamye F. O’Neal ◽  
Garret A. FitzGerald ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Production ◽  
Th1 And Th2 ◽  
Effector Cytokine

scholarly journals CD4 T cells: fates, functions, and faults

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1557-1569 ◽  
Author(s):  
Jinfang Zhu ◽  
William E. Paul
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Production ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Th2 Cells ◽  
Surface Receptors ◽  
The Past ◽  
History Of ◽  
Th1 And Th2

Abstract In 1986, Mosmann and Coffman identified 2 subsets of activated CD4 T cells, Th1 and Th2 cells, which differed from each other in their pattern of cytokine production and their functions. Our understanding of the importance of the distinct differentiated forms of CD4 T cells and of the mechanisms through which they achieve their differentiated state has greatly expanded over the past 2 decades. Today at least 4 distinct CD4 T-cell subsets have been shown to exist, Th1, Th2, Th17, and iTreg cells. Here we summarize much of what is known about the 4 subsets, including the history of their discovery, their unique cytokine products and related functions, their distinctive expression of cell surface receptors and their characteristic transcription factors, the regulation of their fate determination, and the consequences of their abnormal activation.

scholarly journals T cell-intrinsic IL-1R signaling licenses effector cytokine production by memory CD4 T cells

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Aakanksha Jain ◽  
Ran Song ◽  
Edward K. Wakeland ◽  
Chandrashekhar Pasare
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cytokine Production ◽  
Memory Cd4 T Cells ◽  
Effector Cytokine

Cholecystokinin octapeptide regulates the differentiation and effector cytokine production of CD4+ T cells in vitro

2014 ◽  
Vol 20 (2) ◽  
pp. 307-315 ◽  
Author(s):  
Jing-Ge Zhang ◽  
Jun-Xu Liu ◽  
Xian-Xian Jia ◽  
Jing Geng ◽  
Feng Yu ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Production ◽  
Cholecystokinin Octapeptide ◽  
Effector Cytokine

Naïve and Memory CD4+ T Cells Proliferate and Contribute to Cytokine Production in the Human Alloreactive T Cell Response in Vitro.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4983-4983
Author(s):  
Sergio L.R. Martins ◽  
Lisa S. St. John ◽  
Krishna V. Komanduri
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cytokine Production ◽  
Memory T Cells ◽  
Ccr7 Expression ◽  
Alloreactive T Cell ◽  
Memory Cd4 T Cells ◽  
Effector Cytokine

Abstract Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in the setting of allogeneic stem cell transplantation (SCT). We recently developed a cytokine flow cytometry (CFC)-based assay to assess alloreactivity (Martins, et al., Blood 2004). This approach utilizes CFC to facilitate the simultaneous assessment of effector cytokine production and the surface phenotype of responding alloreactive T cells. Recently, studies in murine models have suggested that GVHD may be mediated primarily by naïve T cells and not by memory T cells, raising the possibility that naïve T cell depletion may limit clinical GVHD after human SCT. We sought to assess the independent capability of human naïve and memory T cells to respond functionally to alloantigenic stimulation by CFC. To do this, we purified naive CD4 T cells (CD45RA+CD62L+), memory CD4 T cells (CD4+CD45RA-CD62L+) or naïve-depleted CD4+ T cells (consisting of both CD4+CD45RA-CD62L+ and CD4+CD45RA-CD62L- cells) from fresh healthy donor PBMC using cell sorting. Purified populations were recombined with autologous monocytes and then stimulated with pooled, irradiated mismatched allogeneic stimulator cells, irradiated autologous cells or media. Purified responder cell subpopulations were also labeled with CFSE to facilitate assessment of functional activation and proliferation in the CFSE-marked subsets. Following three and seven day stimulation periods, responder T cells were harvested and incubated in the presence of brefeldin A for 6 hr to facilitate the accumulation of intracellular TNFα, an effector cytokine important in GVHD pathogenesis. We then analyzed the frequencies of responding CFSE-low CD4+ T cells expressing surface differentiation and activation markers, and assessed the co-expression of intracellular TNFα using CFC. We assessed a wide range of T cell surface markers (e.g., CD25, CD38, CD58, CD122, CD45RO, CD62L, and CCR7). By day seven, we consistently observed alloreactive T cell activation in the naïve CD4+ T cell (i.e., CD45RA+CD62L+) compartment. However, purified populations of memory CD4+ T cells also responded to alloreactive stimulation, as assessed by both decreased CFSE staining intensity and by intracellular TNFα production. Amongst cells that were naïve in phenotype prior to stimulation (CD45RA+CD62L+), we observed that those cells that were CFSE-low after stimulation (proliferating cells) downregulated CD45RA and CD62L, consistent with maturation to a memory phenotype. Surprisingly, the expression of the chemokine receptor CCR7, a marker of naïve and central memory T cells also known to be important in lymphoid homing, was altered following allogeneic activation in proliferating (CFSE-low) cells that were originally naïve in phenotype. CCR7 expression increased on a subpopulation of alloreactive cells but decreased on a distinct subset of these cells. Similarly, increases in CCR7 expression were also demonstrated in memory CD4+ T cells following functional activation with alloantigens. In summary, these experiments demonstrate that both naive and memory human T cells responding to allogeneic stimulation are capable of proliferation and effector cytokine production in vitro. Additionally, responding naïve CD4+ T cells lose CD45RA and CD62L expression, consistent with memory maturation, while distinct subsets of these cells increase and decrease their expression of CCR7.

Comparison of In Vitro and In Vivo Effects of Infliximab on Cytokine Production in Proliferating CD4+ T Cells in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 1 (2) ◽  
pp. 122-128
Author(s):  
Syuichi Koarada ◽  
Yuri Sadanaga ◽  
Natsumi Nagao ◽  
Satoko Tashiro ◽  
Rie Suematsu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Cytokine Production

Graft-vs-leukemia activity and graft-vs-host disease induced by allogeneic Th1- and Th2-type CD4+ T cells in mice

2001 ◽  
Vol 2 (2) ◽  
pp. 136-144 ◽  
Author(s):  
Matthias Zeis ◽  
Lutz Uharek ◽  
Götz Hartung ◽  
Bertram Glass ◽  
Jörg Steinmann ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Host Disease ◽  
Graft Vs Host Disease ◽  
Th1 And Th2

scholarly journals SERPINB10 contributes to asthma by inhibiting the apoptosis of allergenic Th2 cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuqing Mo ◽  
Ling Ye ◽  
Hui Cai ◽  
Guiping Zhu ◽  
Jian Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Allergic Asthma ◽  
Cd4 T Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Allergic Inflammation ◽  
Specific Ige ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Th2 Response ◽  
Th1 And Th2

Abstract Background Serine peptidase inhibitor, clade B, member 10 (SERPINB10) contributes to allergic inflammation in asthma. However, its role in the T-helper type 2 (Th2) response of allergic asthma is not known. The goal of this study was to unveil the function of SERPINB10 in the Th2 response of allergic asthma and the mechanism by which SERPINB10 affects the viability of Th2 cells. Methods Th2 cytokines and serum levels of house dust mite (HDM)-specific IgE in bronchoalveolar lavage fluid were examined by ELISA in an HDM-induced asthma model. The number and apoptosis of Th1 and Th2 cells in mouse lungs were measured by flow cytometry. Naïve CD4 T cells from patients with asthma were cultured under appropriate polarizing conditions to generate Th1 and Th2 cells. SERPINB10 expression in polarized Th1 and Th2 cells was quantified by real-time reverse transcription-quantitative polymerase chain reaction. SERPINB10 expression was knocked down in human CD4 T cells with lentivirus. Results Knockdown of SERPINB10 expression significantly diminished HDM-induced Th2 cytokine secretion and level of HDM-specific IgE. After HDM exposure, SERPINB10-knockdown mice had diminished numbers of Th2 cells, but similar numbers of Th1 cells, compared with those in negative-control mice. Th2 cells of SERPINB10-knockdown mice were more susceptible to apoptosis than that of control mice. Stimulating T-cell receptors (TCRs) with anti-CD3 antibody caused upregulation of SERPINB10 expression in polarized Th2 cells, but not polarized Th1 cells. Knockdown of SERPINB10 expression resulted in fewer numbers and greater apoptosis of polarized Th2 cells. Conclusion Our results suggest that SERPINB10 may contribute to allergic inflammation and the Th2 response of asthma by inhibiting the apoptosis of Th2 cells.

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.

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