scholarly journals Signalling through CD28 T-cell activation pathway involves an inositol phospholipid-specific phospholipase C activity

1993 ◽  
Vol 293 (3) ◽  
pp. 835-842 ◽  
Author(s):  
J Nunes ◽  
S Klasen ◽  
M D Franco ◽  
C Lipcey ◽  
C Mawas ◽  
...  
Keyword(s):  
T Cell ◽  
Phospholipase C ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Jurkat Cells ◽  
Cd28 Molecule ◽  
Human T Cell ◽  
Protein Kinase C Inhibitor ◽  
Human T Cell Line

Stimulation of the human T-cell line, Jurkat, by a monoclonal antibody (mAb) directed against the CD28 molecule leads to sustained increases in intracellular levels of Ca2+ ([Ca2+]i); the initial rise in Ca2+ comes from internal stores, followed by Ca2+ entry into the cells. The CD28 molecule also appears to activate polyphosphoinositide (InsPL)-specific phospholipase C (PLC) activity in Jurkat cells, as demonstrated by PtdInsP2 breakdown, InsP3 and 1,2-diacylglycerol generation and PtdIns resynthesis. We also observed that interleukin-2 (IL2) production induced via CD28 triggering was sensitive to a selective protein kinase C inhibitor. Of the four other anti-CD28 mAbs (CD28.2, CD28.4, CD28.5, CD28.6) tested, only one (CD28.5) was unable to generate any InsPL-specific PLC or IL2 secretion. However, the cross-linking of cell-bound CD28.5 with anti-mouse Ig antibodies led to an increase in [Ca2+]i. CD28-molecule clustering in itself appears to be a sufficient signal for induction of PLC activity.

scholarly journals Functional Interactions Between the Thrombin Receptor and the T-Cell Antigen Receptor in Human T-Cell Lines

Blood ◽  
1997 ◽  
Vol 90 (5) ◽  
pp. 1893-1901 ◽  
Author(s):  
David E. Joyce ◽  
Yan Chen ◽  
Rochelle A. Erger ◽  
Gary A. Koretzky ◽  
Steven R. Lentz
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
T Cell Activation ◽  
Cell Activation ◽  
Jurkat Cells ◽  
Thrombin Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Human T Cell ◽  
T Cell Lines

Abstract The proteolytically activated thrombin receptor (TR) is expressed by T lymphocytes, which suggests that thrombin may modulate T-cell activation at sites of hemostatic stress. We examined the relationship between TR function and T-cell activation in the Jurkat human T-cell line and in T-cell lines with defined defects in T-cell antigen receptor (TCR) function. Stimulation with thrombin or the synthetic TR peptide SFLLRN produced intracellular Ca2+ transients in Jurkat cells. As the concentration of TR agonist was increased, peak Ca2+ mobilization increased, but influx of extracellular Ca2+ decreased. TR signaling was enhanced in a TCR-negative Jurkat line and in T-cell lines deficient in the tyrosine kinase lck or the tyrosine phosphatase CD45, both of which are essential for normal TCR function. TCR cross-linking with anti-CD3 IgM desensitized TR signaling in Jurkat cells, but not in CD45-deficient cells. A proteinase-activated receptor (PAR-2)–specific agonist peptide, SLIGKV, produced small Ca2+ transients in both MEG-01 human megakaryocytic cells and Jurkat cells, but was less potent than the TR-specific agonist TFRIFD in both cell types. Like TR signaling, PAR-2 signaling was enhanced in TCR-negative or lck-deficient Jurkat clones. These findings provide evidence for functional cross-talk between proteolytically activated receptors and the TCR.

scholarly journals Submicromolar La3+ concentrations block the calcium release-activated channel, and impair CD69 and CD25 expression in CD3- or thapsigargin-activated Jurkat cells

1996 ◽  
Vol 313 (3) ◽  
pp. 909-913 ◽  
Author(s):  
Claude AUSSEL ◽  
Rachid MARHABA ◽  
Claudette PELASSY ◽  
Jean-Philippe BREITTMAYER
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Calcium Release ◽  
Cell Signalling ◽  
Interleukin 2 ◽  
Jurkat Cells ◽  
T Cell Signalling ◽  
A Chain ◽  
20 Nm

The calcium release-activated channel (CRAC) opened in Jurkat cells activated either with CD3 monoclonal antibody or the endoplasmic reticulum Ca2+-ATPase blocker, thapsigargin, is blocked by La3+ with an IC50 of 20 nM. Similarly, the entry of Mn2+, used as a surrogate for Ca2+, is also blocked by submicromolar La3+ concentrations. La3+ seems to play its role simply by plugging the CRAC because this ion does not penetrate the cells, as demonstrated by chelation experiments with EGTA. Blocking the Ca2+ influx in activated Jurkat cells results in a lack of expression of CD25, a chain of the interleukin-2 receptor and of CD69, a marker of T-cell activation. By contrast, the very early steps of the T-cell signalling pathway such as the release of Ca2+ from intracellular stores and the subsequent inhibition of phosphatidylserine synthesis are not affected by La3+.

The C-class chemokine, lymphotactin, impairs the induction of Th1-type lymphokines in human CD4+ T cells

Blood ◽  
2000 ◽  
Vol 96 (2) ◽  
pp. 420-428 ◽  
Author(s):  
Chantal Cerdan ◽  
Edgar Serfling ◽  
Daniel Olive
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Jurkat Cells ◽  
Cd4 T Cell ◽  
T Cell Proliferation ◽  
Human T Cell

Abstract Chemokines are involved in the regulation of leukocyte migration and for some of them, T-cell costimulation. To date, the only direct property of lymphotactin (Lptn), the unique member of the C class of chemokines, consists of T-cell chemoattraction. This report describes a novel function for Lptn in human T-lymphocyte biology, by demonstrating the direct ability of Lptn to both inhibit and costimulate CD4+ and CD8+ T-cell activation, respectively. Lptn but not RANTES inhibited CD4+ T-cell proliferation, through a decreased production of Th1 (interleukin [IL]-2, interferon [IFN]-γ) but not Th2 (IL-4, IL-13) lymphokines, and decreased IL-2R expression. Transfections in Jurkat cells showed a Lptn-mediated transcriptional down-regulation of gene-promoter activities specific for Th1-type lymphokines, as well as of nuclear factor of activated T cells (NF-AT) but not AP-1 or NF-ΚB enhancer activities. This suppressive action of Lptn could be compensated by overexpression of NF-ATc but not NF-ATp. CD4+ T-cell proliferation was completely restored by exogenous IL-2 or reversed by pertussis toxin, wortmannin, and genistein, suggesting the involvement of multiple partners in Lptn signaling. In contrast to CD4+ cells, Lptn exerted a potent costimulatory activity on CD8+ T-cell proliferation and IL-2 secretion. These data provide important insights into the role of Lptn in differential regulation of normal human T-cell activation and its possible implication in immune response disorders.

A yeast-based screening system identified bakkenolide B contained in Petasites japonicus as an inhibitor of interleukin-2 production in a human T cell line

2021 ◽  
Author(s):  
Shota Uesugi ◽  
Mayuka Hakozaki ◽  
Yuko Kanno ◽  
Honoka Takahashi ◽  
Yui Kudo ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Screening Method ◽  
Interleukin 2 ◽  
Jurkat Cells ◽  
Yeast Cells ◽  
Wild Plant ◽  
Human T Cell ◽  
Petasites Japonicus ◽  
Human T Cell Line

Abstract Ca2+ signaling is related to various diseases such as allergies, diabetes, and cancer. We explored Ca2+ signaling inhibitors in natural resources using a yeast-based screening method, and found bakkenolide B from the flower buds of edible wild plant, Petasites japonicus, using the YNS17 strain (zds1Δ erg3Δ pdr1/3Δ). Bakkenolide B exhibited growth-restoring activity against the YNS17 strain and induced Li+ sensitivity of wild-type yeast cells, suggesting that it inhibits the calcineurin pathway. Additionally, bakkenolide B inhibited interleukin-2 production at gene and protein levels in Jurkat cells, a human T cell line, but not the in vitro phosphatase activity of human recombinant calcineurin, an upstream regulator of interleukin-2 production. Furthermore, bakkenolide A showed weak activity in YNS17 and Jurkat cells compared with bakkenolide B. These findings revealed new biological effects and the structure-activity relationships of bakkenolides contained in Petasites japonicus as inhibitors of interleukin-2 production in human T cells.

scholarly journals Early signaling defects in human T cells anergized by T cell presentation of autoantigen.

1992 ◽  
Vol 176 (1) ◽  
pp. 177-186 ◽  
Author(s):  
J M LaSalle ◽  
P J Tolentino ◽  
G J Freeman ◽  
L M Nadler ◽  
D A Hafler
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Intact Protein ◽  
Peptide Antigen ◽  
L Cell ◽  
Human T Cell

Major histocompatibility complex class II-positive human T cell clones are nontraditional antigen-presenting cells (APCs) that are able to simultaneously present and respond to peptide or degraded antigen, but are unable to process intact protein. Although T cell presentation of peptide antigen resulted in a primary proliferative response, T cells that had been previously stimulated by T cells presenting antigen were completely unresponsive to antigen but not to interleukin 2 (IL-2). In contrast, peptide antigen presented by B cells or DR2+ L cell transfectants resulted in T cell activation and responsiveness to restimulation. The anergy induced by T cell presentation of peptide could not be prevented by the addition of either autologous or allogeneic B cells or B7+ DR2+ L cell transfectants, suggesting that the induction of anergy could occur in the presence of costimulation. T cell anergy was induced within 24 h of T cell presentation of antigen and was long lasting. Anergized T cells expressed normal levels of T cell receptor/CD3 but were defective in their ability to release [Ca2+]i to both alpha CD3 and APCs. Moreover, anergized T cells did not proliferate to alpha CD2 monoclonal antibodies or alpha CD3 plus phorbol myristate acetate (PMA), nor did they synthesize IL-2, IL-4, or interferon gamma mRNA in response to either peptide or peptide plus PMA. In contrast, ionomycin plus PMA induced both normal proliferative responses and synthesis of cytokine mRNA, suggesting that the signaling defect in anergized cells occurs before protein kinase C activation and [Ca2+]i release.

The C-class chemokine, lymphotactin, impairs the induction of Th1-type lymphokines in human CD4+ T cells

Blood ◽  
2000 ◽  
Vol 96 (2) ◽  
pp. 420-428 ◽  
Author(s):  
Chantal Cerdan ◽  
Edgar Serfling ◽  
Daniel Olive
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Jurkat Cells ◽  
Cd4 T Cell ◽  
T Cell Proliferation ◽  
Human T Cell

Chemokines are involved in the regulation of leukocyte migration and for some of them, T-cell costimulation. To date, the only direct property of lymphotactin (Lptn), the unique member of the C class of chemokines, consists of T-cell chemoattraction. This report describes a novel function for Lptn in human T-lymphocyte biology, by demonstrating the direct ability of Lptn to both inhibit and costimulate CD4+ and CD8+ T-cell activation, respectively. Lptn but not RANTES inhibited CD4+ T-cell proliferation, through a decreased production of Th1 (interleukin [IL]-2, interferon [IFN]-γ) but not Th2 (IL-4, IL-13) lymphokines, and decreased IL-2R expression. Transfections in Jurkat cells showed a Lptn-mediated transcriptional down-regulation of gene-promoter activities specific for Th1-type lymphokines, as well as of nuclear factor of activated T cells (NF-AT) but not AP-1 or NF-ΚB enhancer activities. This suppressive action of Lptn could be compensated by overexpression of NF-ATc but not NF-ATp. CD4+ T-cell proliferation was completely restored by exogenous IL-2 or reversed by pertussis toxin, wortmannin, and genistein, suggesting the involvement of multiple partners in Lptn signaling. In contrast to CD4+ cells, Lptn exerted a potent costimulatory activity on CD8+ T-cell proliferation and IL-2 secretion. These data provide important insights into the role of Lptn in differential regulation of normal human T-cell activation and its possible implication in immune response disorders.

scholarly journals SHP2-interacting Transmembrane Adaptor Protein (SIT), A Novel Disulfide-linked Dimer Regulating Human T Cell Activation

1999 ◽  
Vol 189 (8) ◽  
pp. 1181-1194 ◽  
Author(s):  
Anne Marie-Cardine ◽  
Henning Kirchgessner ◽  
Eddy Bruyns ◽  
Andrej Shevchenko ◽  
Matthias Mann ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Tyrosine Phosphatase ◽  
Adaptor Protein ◽  
Adaptor Proteins ◽  
Sh2 Domain ◽  
Jurkat Cells ◽  
Activated T Cells ◽  
Human T Cell

T lymphocytes express several low molecular weight transmembrane adaptor proteins that recruit src homology (SH)2 domain–containing intracellular molecules to the cell membrane via tyrosine-based signaling motifs. We describe here a novel molecule of this group termed SIT (SHP2 interacting transmembrane adaptor protein). SIT is a disulfide-linked homodimeric glycoprotein that is expressed in lymphocytes. After tyrosine phosphorylation by src and possibly syk protein tyrosine kinases SIT recruits the SH2 domain–containing tyrosine phosphatase SHP2 via an immunoreceptor tyrosine-based inhibition motif. Overexpression of SIT in Jurkat cells downmodulates T cell receptor– and phytohemagglutinin-mediated activation of the nuclear factor of activated T cells (NF-AT) by interfering with signaling processes that are probably located upstream of activation of phospholipase C. However, binding of SHP2 to SIT is not required for inhibition of NF-AT induction, suggesting that SIT not only regulates NF-AT activity but also controls NF-AT unrelated pathways of T cell activation involving SHP2.

scholarly journals In vivo and in vitro phosphorylation of annexin II in T cells: potential regulation by annexin V

1995 ◽  
Vol 310 (1) ◽  
pp. 243-248 ◽  
Author(s):  
T Dubois ◽  
J P Oudinet ◽  
F Russo-Marie ◽  
B Rothhut
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cellular Proliferation ◽  
Large Family ◽  
Jurkat Cells ◽  
Human T Cell

In order to understand how signal transduction occurs during T cell activation, it is necessary to identify the key regulatory molecules whose function is influenced by phosphorylation. Annexins II (A-II) and V (A-V) belong to a large family of Ca(2+)-dependent phospholipid-binding proteins. Among many putative functions, annexins may be involved in signal transduction during cellular proliferation and differentiation. In the present study we show that A-II is phosphorylated in vivo in the Jurkat human T cell line. Indeed, A-II is phosphorylated after stimulation by phorbol myristate acetate and on serine residues after T cell antigen receptor (TcR) stimulation. In cytosol from Jurkat cells, A-II is phosphorylated only by Ca2+/phospholipid-stimulated kinases such as Ca(2+)-dependent protein kinases C (cPKCs). A-V inhibits the phosphorylation of A-II and other substrates of cPKCs and has no effect on kinases activated only by phospholipids. In conclusion, A-II is phosphorylated both in vitro and in vivo in Jurkat cells, and may play a role as a substrate during signal transduction in lymphocytes via the TcR through the PKC pathway. On the other hand, A-V could act as a potent modulator of cPKCs in Jurkat cells.

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