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.

Oncogenic activation of the Lck protein accompanies translocation of the LCK gene in the human HSB2 T-cell leukemia

1994 ◽  
Vol 14 (4) ◽  
pp. 2429-2437
Author(s):  
D D Wright ◽  
B M Sefton ◽  
M P Kamps
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
T Cell Activation ◽  
Cell Activation ◽  
Chromosomal Translocation ◽  
Cell Receptor ◽  
Kinase Domain ◽  
3T3 Fibroblasts ◽  
Human T Cell ◽  
T Cell Lines

The tyrosine protein kinase p56lck transduces signals important for antigen-induced T-cell activation. In transgenic mice, p56lck is oncogenic when overexpressed or expressed as a mutant, catalytically activated enzyme. In humans, the LCK gene is located at the breakpoint of the t(1;7)(p34;q34) chromosomal translocation. This translocation positions the beta T-cell receptor constant region enhancer upstream of the LCK gene without interrupting the LCK coding sequences, and a translocation of this sort occurs in both the HSB2 and the SUP-T-12 T-cell lines. We have found that, although the level of the p56lck protein in HSB2 cells is elevated approximately 2-fold in comparison with that in normal T-cell lines, total cellular tyrosine protein phosphorylation is elevated approximately 10-fold. Increased levels of phosphotyrosine in HSB2 cells resulted from mutations in the LCK gene that activated its function as a phosphotransferase and converted it into a dominant transforming oncogene. The oncogenic p56lck in HSB2 cells contained one amino acid substitution within the CD4/CD8-binding domain, two substitutions in the kinase domain, and an insertion of Gln-Lys-Pro (QKP) between the SH2 and kinase domains. In NIH 3T3 fibroblasts, three of these mutations cooperated to produce the fully oncogenic form of this p56lck variant. These results suggest that mutation of LCK may contribute to some human T-cell leukemias.

scholarly journals Oncogenic activation of the Lck protein accompanies translocation of the LCK gene in the human HSB2 T-cell leukemia.

1994 ◽  
Vol 14 (4) ◽  
pp. 2429-2437 ◽  
Author(s):  
D D Wright ◽  
B M Sefton ◽  
M P Kamps
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
T Cell Activation ◽  
Cell Activation ◽  
Chromosomal Translocation ◽  
Cell Receptor ◽  
Kinase Domain ◽  
3T3 Fibroblasts ◽  
Human T Cell ◽  
T Cell Lines

The tyrosine protein kinase p56lck transduces signals important for antigen-induced T-cell activation. In transgenic mice, p56lck is oncogenic when overexpressed or expressed as a mutant, catalytically activated enzyme. In humans, the LCK gene is located at the breakpoint of the t(1;7)(p34;q34) chromosomal translocation. This translocation positions the beta T-cell receptor constant region enhancer upstream of the LCK gene without interrupting the LCK coding sequences, and a translocation of this sort occurs in both the HSB2 and the SUP-T-12 T-cell lines. We have found that, although the level of the p56lck protein in HSB2 cells is elevated approximately 2-fold in comparison with that in normal T-cell lines, total cellular tyrosine protein phosphorylation is elevated approximately 10-fold. Increased levels of phosphotyrosine in HSB2 cells resulted from mutations in the LCK gene that activated its function as a phosphotransferase and converted it into a dominant transforming oncogene. The oncogenic p56lck in HSB2 cells contained one amino acid substitution within the CD4/CD8-binding domain, two substitutions in the kinase domain, and an insertion of Gln-Lys-Pro (QKP) between the SH2 and kinase domains. In NIH 3T3 fibroblasts, three of these mutations cooperated to produce the fully oncogenic form of this p56lck variant. These results suggest that mutation of LCK may contribute to some human T-cell leukemias.

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.

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.

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