scholarly journals Trogocytosis-Mediated Intracellular Signaling in CD4+T Cells Drives TH2-Associated Effector Cytokine Production and Differentiation

2019 ◽  
Vol 202 (10) ◽  
pp. 2873-2887 ◽  
Author(s):  
Jim Reed ◽  
Scott A. Wetzel
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Intracellular Signaling ◽  
Cytokine Production ◽  
Effector Cytokine

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

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

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

scholarly journals CRTAM determines the CD4+ cytotoxic T lymphocyte lineage

2015 ◽  
Vol 213 (1) ◽  
pp. 123-138 ◽  
Author(s):  
Arata Takeuchi ◽  
Mohamed El Sherif Gadelhaq Badr ◽  
Kosuke Miyauchi ◽  
Chitose Ishihara ◽  
Reiko Onishi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic Activity ◽  
Cd4 T Cells ◽  
Intracellular Signaling ◽  
Ectopic Expression ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Ifn Γ

Naive T cells differentiate into various effector T cells, including CD4+ helper T cell subsets and CD8+ cytotoxic T cells (CTL). Although cytotoxic CD4+ T cells (CD4+CTL) also develop from naive T cells, the mechanism of development is elusive. We found that a small fraction of CD4+ T cells that express class I–restricted T cell–associated molecule (CRTAM) upon activation possesses the characteristics of both CD4+ and CD8+ T cells. CRTAM+ CD4+ T cells secrete IFN-γ, express CTL-related genes, such as eomesodermin (Eomes), Granzyme B, and perforin, after cultivation, and exhibit cytotoxic function, suggesting that CRTAM+ T cells are the precursor of CD4+CTL. Indeed, ectopic expression of CRTAM in T cells induced the production of IFN-γ, expression of CTL-related genes, and cytotoxic activity. The induction of CD4+CTL and IFN-γ production requires CRTAM-mediated intracellular signaling. CRTAM+ T cells traffic to mucosal tissues and inflammatory sites and developed into CD4+CTL, which are involved in mediating protection against infection as well as inducing inflammatory response, depending on the circumstances, through IFN-γ secretion and cytotoxic activity. These results reveal that CRTAM is critical to instruct the differentiation of CD4+CTL through the induction of Eomes and CTL-related gene.

scholarly journals Sonic Hedgehog Signaling Modulates Activation of and Cytokine Production by Human Peripheral CD4+ T Cells

2002 ◽  
Vol 169 (10) ◽  
pp. 5451-5457 ◽  
Author(s):  
Gareth A. Stewart ◽  
Jacqueline A. Lowrey ◽  
Sonia J. Wakelin ◽  
Paul M. Fitch ◽  
Susannah Lindey ◽  
...  
Keyword(s):  
T Cells ◽  
Sonic Hedgehog ◽  
Cd4 T Cells ◽  
Hedgehog Signaling ◽  
Cytokine Production ◽  
Sonic Hedgehog Signaling

scholarly journals Cytokine production in ex-vivo stimulated fresh and cryopreserved T-cells

2021 ◽  
Vol 67 (2) ◽  
pp. 95-101
Author(s):  
Monica Vuță ◽  
Ionela-Maria Cotoi ◽  
Ion Bogdan Mănescu ◽  
Doina Ramona Manu ◽  
Minodora Dobreanu
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Ex Vivo ◽  
Gradient Centrifugation ◽  
Intracellular Cytokine Staining ◽  
Interleukin 2 ◽  
Middle Aged

Abstract Objective: In vitro cytokine production by peripheral blood mononuclear cells (PBMCs) is an important and reliable measure of immunocompetence. PBMC can be stimulated directly after isolation or frozen for later use. However, cryopreservation may affect cell recovery, viability and functionality. This study aims to investigate cytokine synthesis in ex-vivo stimulated fresh and cryopreserved CD4+ and CD4- T cells. Methods: PBMCs were obtained by Ficoll gradient centrifugation from heparinized peripheral blood of 6 middle-aged clinically healthy subjects. Half of these cells (labeled “Fresh”) was further processed and the other half (labeled “Cryo”) was cryopreserved at -140°C for up to 3 months. Fresh-PBMCs were activated with Phorbol-Myristate-Acetate/Ionomycin/Monensin for 5 hours immediately after isolation while Cryo-PBMCs were identically activated after thawing and cell resting. Activated cells were fixed, permeabilized and intracellular cytokine staining was performed using Phycoerythrin (PE)-conjugated antibodies for Interleukin-2 (IL-2), Tumor Necrosis Factor-alpha (TNF-a), and Interferon-gamma (IFN-g). All samples were analyzed within 24 hours by flow cytometry. Results: Both Fresh and Cryo CD3+CD4+/CD3+CD4- sub-populations partially produced each of the three cytokines. A higher percentage of CD4+ T cells produced IL-2 and TNF-a and a greater percentage of CD4- T cells were found to produce IFN-g. A significantly higher percentage of Cryo-lymphocytes was shown to produce TNF-a in both CD3+CD4+ (31.4% vs 24.9%, p=0.031) and CD3+CD4- (22.7% vs 17.9%, p=0.031) subpopulations. No notable difference was found for IL-2 and IFN-g production between Fresh and Cryo T cells. Conclusion: Cryopreservation for up to 3 months significantly increases TNF-a production of T-cells in clinically healthy middle-aged subjects.

scholarly journals Generation of a Novel T Cell Specific Interleukin-1 Receptor Type 1 Conditional Knock Out Mouse Reveals Intrinsic Defects in Survival, Expansion and Cytokine Production of CD4 T Cells

PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0161505 ◽  
Author(s):  
Ilgiz A. Mufazalov ◽  
Tommy Regen ◽  
Carsten Schelmbauer ◽  
Janina Kuschmann ◽  
Alisa M. Muratova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cytokine Production ◽  
Interleukin 1 ◽  
Receptor Type ◽  
Intrinsic Defects ◽  
Knock Out ◽  
Knock Out Mouse
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