scholarly journals Functional analysis of c-Myb protein in T-lymphocytic cell lines shows that it trans-activates the c-myc promoter

1990 ◽  
Vol 10 (11) ◽  
pp. 5747-5752
Author(s):  
J L Evans ◽  
T L Moore ◽  
W M Kuehl ◽  
T Bender ◽  
J P Ting
Keyword(s):  
T Cell ◽  
Interleukin 2 ◽  
Expression Plasmid ◽  
Protein Coding ◽  
Lymphocytic Cell ◽  
Frameshift Mutant ◽  
Myc Gene ◽  
Hybrid Construct ◽  
Myb Protein

The function of c-Myb protein was revealed by transfecting an expression vector containing the entire c-Myb protein-coding sequence into the murine CTLL-2 T-cell line. Expressions of high levels of c-Myb protein did not alter the expression of several T-cell markers, c-fos mRNA expression, responses to interleukin-2, and growth characteristics of these cells. Interestingly, expression of the c-myc gene was drastically increased in this clone. Further, the c-myb expression plasmid, but not a frameshift mutant of c-myb, enhanced the expression of a hybrid construct of c-myc promoter linked to a reporter gene by 8- to 14-fold. These results demonstrate a role of c-Myb protein in c-myc gene expression.

scholarly journals Functional analysis of c-Myb protein in T-lymphocytic cell lines shows that it trans-activates the c-myc promoter.

1990 ◽  
Vol 10 (11) ◽  
pp. 5747-5752 ◽  
Author(s):  
J L Evans ◽  
T L Moore ◽  
W M Kuehl ◽  
T Bender ◽  
J P Ting
Keyword(s):  
T Cell ◽  
Interleukin 2 ◽  
Expression Plasmid ◽  
Protein Coding ◽  
Lymphocytic Cell ◽  
Frameshift Mutant ◽  
Myc Gene ◽  
Hybrid Construct ◽  
Myb Protein

The function of c-Myb protein was revealed by transfecting an expression vector containing the entire c-Myb protein-coding sequence into the murine CTLL-2 T-cell line. Expressions of high levels of c-Myb protein did not alter the expression of several T-cell markers, c-fos mRNA expression, responses to interleukin-2, and growth characteristics of these cells. Interestingly, expression of the c-myc gene was drastically increased in this clone. Further, the c-myb expression plasmid, but not a frameshift mutant of c-myb, enhanced the expression of a hybrid construct of c-myc promoter linked to a reporter gene by 8- to 14-fold. These results demonstrate a role of c-Myb protein in c-myc gene expression.

scholarly journals The role of Raf-1 in the regulation of extracellular signal-regulated kinase 2 by the T cell antigen receptor.

1994 ◽  
Vol 180 (1) ◽  
pp. 401-406 ◽  
Author(s):  
M Izquierdo ◽  
S Bowden ◽  
D Cantrell
Keyword(s):  
T Cells ◽  
T Cell ◽  
Map Kinases ◽  
Interleukin 2 ◽  
Antigen Receptor ◽  
T Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Constitutively Active

Triggering of the T cell antigen receptor (TCR) complex activates the serine/threonine kinase Raf-1 whose function is necessary for TCR induction of the interleukin 2 gene. Raf-1 has been identified as a candidate mitogen-activated protein (MAP) kinase kinase kinase (MKKK) and thus has the potential to couple the TCR to the activation of the MAP kinases such as ERK2. In the present study, the role of Raf-1 in ERK2 regulation of ERK2 in T cells has been explored. A constitutively active Raf-1 kinase, v-raf, or a dominant inhibitory Raf-1 mutant were expressed transiently from the pEF BOS vector in Jurkat cells and the effects of these Raf-1 mutants on a coexpressed ERK2 reporter was assessed. The action of the constitutively active Raf-1 was to stimulate the ERK2 kinase, whereas the dominant negative version of Raf-1 inhibited the ERK2 activation induced by triggering of the TCR. These data indicate a role for Raf-1 in the regulation of ERK2 in T cells.

Mechanisms of Interleukin-2-Mediated Signaling and role of Calcium in T cell Mitogenesis

1985 ◽  
Vol 14 (5) ◽  
pp. 435-442 ◽  
Author(s):  
Hiroshi Komada ◽  
Hiroshi Nakabayashi ◽  
Masayuki Hara ◽  
Masashi Sawada ◽  
Takao Takahashi ◽  
...  
Keyword(s):  
T Cell ◽  
Interleukin 2

scholarly journals Role of A2a Extracellular Adenosine Receptor-Mediated Signaling in Adenosine-Mediated Inhibition of T-Cell Activation and Expansion

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1600-1610 ◽  
Author(s):  
Steve Huang ◽  
Sergey Apasov ◽  
Masahiro Koshiba ◽  
Michail Sitkovsky
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Adenosine Receptors ◽  
Purinergic Receptors ◽  
Interleukin 2 ◽  
Strong Inhibition ◽  
Extracellular Adenosine ◽  
A2a Receptor ◽  
Adenosine Deaminase Activity

Abstract Accumulation of adenosine and of deoxyadenosine in the absence of adenosine deaminase activity (ADA) activity results in lymphocyte depletion and in severe combined immunodeficiency (ADA SCID), which is currently explained by direct cell death-causing effects of intracellular products of adenosine metabolism. We explored the alternative mechanisms of peripheral T-cell depletion as due to inhibition of T-cell expansion by extracellular adenosine-mediated signaling through purinergic receptors. The strong inhibition of the T-cell receptor (TCR)-triggered proliferation and of upregulation of interleukin-2 receptor α chain (CD25) molecules, but not the direct lymphotoxicity, were observed at low concentrations of extracellular adenosine. These effects of extracellular adenosine (Ado) are likely to be mediated by A2a receptor-mediated signaling rather than by intracellular toxicity of adenosine catabolites, because (1) poorly metabolized adenosine analogs cause the accumulation of cAMP and strong inhibition of TCR-triggered CD25 upregulation; (2) the A2a, but not the A1 or A3, receptors are the major expressed and functionally coupled adenosine receptors in mouse peripheral T and B lymphocytes, and the adenosine-induced cAMP accumulation in lymphocytes correlates with the expression of A2a receptors; (3) the specific agonist of A2a receptor, CGS21680, induces increases in [cAMP]i in lymphocytes, whereas the specific antagonist of A2a receptor, CSC, inhibits the effects of Ado and CGS21680; and (4) the increases in [cAMP]i mimic the adenosine-induced inhibition of TCR-triggered CD25 upregulation and splenocyte proliferation. These studies suggest the possible role of adenosine receptors in the regulation of lymphocyte expansion and point to the downregulation of A2a purinergic receptors on T cells as a potentially attractive pharmacologic target.

Role of C3b receptors in the enhancement of interleukin-2-dependent T-cell proliferation

1984 ◽  
Vol 21 (12) ◽  
pp. 1215-1221 ◽  
Author(s):  
Anna Erdei ◽  
E. Spaeth ◽  
J. Alsenz ◽  
E. Rüde ◽  
T. Schulz ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Interleukin 2 ◽  
T Cell Proliferation

The ζ Isoform of Protein Kinase C Controls Interleukin-2-Mediated Proliferation in a Murine T Cell Line: Evidence for an Additional Role of Protein Kinase C ϵ and β

1995 ◽  
Vol 218 (1) ◽  
pp. 105-113 ◽  
Author(s):  
Javier Gómez ◽  
Christina Pitton ◽  
Alphonse Garcı́a ◽  
Ana Martinez De Aragón ◽  
Augusto Silva ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
T Cell ◽  
Protein Kinase ◽  
Cell Line ◽  
Interleukin 2 ◽  
Kinase C ◽  
Additional Role

An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes

Blood ◽  
2010 ◽  
Vol 115 (2) ◽  
pp. 265-273 ◽  
Author(s):  
Graziella Curtale ◽  
Franca Citarella ◽  
Claudia Carissimi ◽  
Marina Goldoni ◽  
Nicoletta Carucci ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Activation Induced Cell Death

Abstract Activation of the T cell–mediated immune response has been associated with changes in the expression of specific microRNAs (miRNAs). However, the role of miRNAs in the development of an effective immune response is just beginning to be explored. This study focuses on the functional role of miR-146a in T lymphocyte–mediated immune response and provides interesting clues on the transcriptional regulation of miR-146a during T-cell activation. We show that miR-146a is low in human naive T cells and is abundantly expressed in human memory T cells; consistently, miR-146a is induced in human primary T lymphocytes upon T-cell receptor (TCR) stimulation. Moreover, we identified NF-kB and c-ETS binding sites as required for the induction of miR-146a transcription upon TCR engagement. Our results demonstrate that several signaling pathways, other than inflammation, are influenced by miR-146a. In particular, we provide experimental evidence that miR-146a modulates activation-induced cell death (AICD), acting as an antiapoptotic factor, and that Fas-associated death domain (FADD) is a target of miR-146a. Furthermore, miR-146a enforced expression impairs both activator protein 1 (AP-1) activity and interleukin-2 (IL-2) production induced by TCR engagement, thus suggesting a role of this miRNA in the modulation of adaptive immunity.

Dendritic cell-derived IL-2 production is regulated by IL-15 in humans and in mice

Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 697-702 ◽  
Author(s):  
Sonia Feau ◽  
Valeria Facchinetti ◽  
Francesca Granucci ◽  
Stefania Citterio ◽  
David Jarrossay ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Molecular Mechanisms ◽  
Interleukin 2 ◽  
Adaptive Immune ◽  
Deficient Mice ◽  
Mouse System

Abstract Dendritic cells (DCs) are involved in the initiation and regulation of innate and adaptive immune responses. Several molecular mechanisms regulate these diverse DC functions, and we have previously reported that mouse dendritic cells (mDCs) can produce interleukin-2 (IL-2) in vitro and in vivo, in response to microbial activation and T-cell-mediated stimuli. This property is shared by different DC subtypes, including Langerhans cells. Here we show that, on appropriate stimulation, human DCs, both plasmacytoid and myeloid subtypes, also express IL-2. Interestingly, the production of IL-2 by myeloid DCs is induced by T-cell-mediated stimuli and depends on the presence of IL-15. The key role of this cytokine in regulating IL-2 production was also confirmed in the mouse system. In particular, we could show that DCs from IL-15-deficient mice were strongly impaired in the ability to produce IL-2 after interactions with different microbial stimuli. Our results indicate that DC-produced IL-2 is tightly coregulated with the expression of IL-15.

scholarly journals The T-cell CD2 determinant mediates inhibition of erythropoiesis by the lymphokine cascade

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 770-775 ◽  
Author(s):  
S Burdach ◽  
M Shatsky ◽  
B Wagenhorst ◽  
L Levitt
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interleukin 2 ◽  
Receptor Expression ◽  
Isotype Control ◽  
Isotype Control Antibody ◽  
Dependent Inhibition ◽  
Neutralizing Monoclonal Antibody ◽  
Dose Dependent Inhibition

Abstract We examined the role of the T-cell antigen CD2 in the regulation of erythropoiesis by the lymphokine cascade. T-cell interleukin-2 (IL-2) receptors (p55) were induced via triggering of the antigen receptor- associated CD3 epitope. Before CD3 triggering T cells were preincubated with a CD2-blocking (Leu-5b) or isotype control antibody. T-cell pellets were employed during incubation to facilitate interaction between T-cell LFA-3 and CD2. CD2 blockade caused a 66% to 79% inhibition of p55 expression after three to six days of culture with IL- 2. Next we assessed the effect of CD2 blockade on IL-2. Next we assessed the effect of CD2 blockade on IL-2-induced inhibition of BFU-E in autologous cocultures containing CD3-triggered T cells. IL-2 caused a dose-dependent inhibition (52% to 92%) of BFU-E in the presence but not in the absence of CD3-triggered T cells. T-cell CD2 blockade prior to CD3 triggering caused a 65% to 87% abrogation of IL-2-induced inhibition of BFU-E at 10 to 10(2) U/mL IL-2. Preincubation of CD3- triggered T cells with isotype control antibody had no effect on IL-2- induced erythroid inhibition. Day 3 supernatants from CD3-triggered T cells or CD2-blocked, CD3-triggered T cells established in the presence of IL-2 were next assessed for modulation of BFU-E. CD3-triggered T- cell supernatants caused a 77% +/- 9% inhibition of BFU-E. Blockade of CD2 caused a 95% abrogation of T-cell-mediated BFU-E inhibition. In addition, CD2 blockade reduced interferon-gamma (IF gamma) release (84 to 128 U/mL) from CD3-triggered T cells by 81% at day 3 of culture. In control experiments, the addition of IF gamma-neutralizing monoclonal antibody to CD3-triggered T-cell supernatant established in the presence of IL-2 caused 75% abrogation of IL-2 inhibition of BFU-E. We conclude that blockade of the CD2 T-cell determinant induces down modulation of (a) T-cell p55 IL-2 receptor expression, (b) IL-2-induced inhibition of BFU-E, and (c) IL-2-induced marrow T-cell IF gamma release. These data suggest that the T-cell CD2 determinant can exert a regulatory effect on the control of erythropoiesis by the lymphokine cascade.

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