Underlying purinergic signaling contributes to T lymphocyte activation in tissue repair. Focus on “Shockwaves increase the T-cell proliferation and IL-2 expression through ATP release, P2X7 receptors, and FAK activation”

2010 ◽  
Vol 298 (3) ◽  
pp. C446-C447 ◽  
Author(s):  
Erik M. Schwiebert
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
T Lymphocyte ◽  
Tissue Repair ◽  
Purinergic Signaling ◽  
Atp Release ◽  
Lymphocyte Activation ◽  
T Cell Proliferation ◽  
P2x7 Receptors ◽  
T Lymphocyte Activation

scholarly journals T-cell mediated autoimmunity to the insulinoma-associated protein 2 islet tyrosine phosphatase in type 1 diabetes mellitus

1999 ◽  
pp. 272-278 ◽  
Author(s):  
F Dotta ◽  
S Dionisi ◽  
V Viglietta ◽  
C Tiberti ◽  
MC Matteoli ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Type 1 Diabetes ◽  
T Cell ◽  
T Lymphocyte ◽  
Tyrosine Phosphatase ◽  
T Cell Response ◽  
T Cell Proliferation ◽  
Diabetic Patients ◽  
Hla Dr

The target molecules of the T-cell response in type 1 diabetes, despite their pathogenic importance, remain largely uncharacterized, especially in humans. Interestingly, molecules such as insulin and glutamic acid decarboxylase (GAD) have been shown to be a target not only of autoantibodies, but also of autoreactive T-lymphocytes both in man and in the non-obese diabetic (NOD) mouse. In the present study we aimed to determine the existence of a specific T-cell response towards the insulinoma-associated protein 2 (IA-2) islet tyrosine phosphatase, a recently identified autoantigen which is the target of autoantibodies strongly associated with diabetes development. Human recombinant IA-2 produced in Escherichia coli, was tested for its reactivity with peripheral blood lymphocytes obtained from 16 newly diagnosed type 1 diabetic patients and from 25 normal controls, 15 of whom were HLA-DR-matched. A T-cell proliferation assay was performed in triplicate employing freshly isolated cells in the absence or in the presence of the antigen to be tested (at two different concentrations: 2 microg/ml and 10 microg/ml). A specific T-cell proliferation (defined as a stimulation index (S.I.) >/=3) was observed against IA-2 used at a concentration of 10 microg/ml (but not of 2 microg/ml) in 8/16 diabetic patients, in 1/15 HLA-DR-matched control subjects (P<0.01 by Fisher exact test) and in 0/10 of the remaining normal individuals. A statistically significant difference (P<0.003 by Mann-Whitney U test) was also observed in S.I. values between patients (3.1+/-1.4) and HLA-DR-matched controls (1.7+/-0.54) employing IA-2 at a concentration of 10 microg/ml. However, when IA-2 was used at a concentration of 2 microg/ml, the difference in S. I. between patients (1.65+/-0.8) and controls (1.0+/-0.3) did not reach statistical significance. In conclusion, these data show the presence of a specific, dose-dependent T-lymphocyte response against the IA-2 islet tyrosine phosphatase at the onset of type 1 diabetes. Consequently, this molecule appears to be a target not only at the B-lymphocyte but also at the T-lymphocyte level, reinforcing the potential pathogenic role of this autoantigen in the islet destructive process.

Immunodeficiency with low expression of the T cell receptor/CD3 complex. Effect on T lymphocyte activation

1991 ◽  
Vol 21 (7) ◽  
pp. 1641-1647 ◽  
Author(s):  
Françoise Le Deist ◽  
Gabriela Thoenes ◽  
José Corado ◽  
Barbara Lisowska-Grospierre ◽  
Alain Fischer
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Lymphocyte ◽  
Lymphocyte Activation ◽  
Cell Receptor ◽  
Complex Effect ◽  
T Lymphocyte Activation ◽  
Low Expression

scholarly journals Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection.

1989 ◽  
Vol 170 (1) ◽  
pp. 145-161 ◽  
Author(s):  
R Patarca ◽  
G J Freeman ◽  
R P Singh ◽  
F Y Wei ◽  
T Durfee ◽  
...  
Keyword(s):  
T Cell ◽  
Bacterial Infection ◽  
T Lymphocyte ◽  
Inbred Mouse ◽  
Genetic Resistance ◽  
Lymphocyte Activation ◽  
Cellular Adhesion ◽  
Mouse Strains ◽  
T Lymphocyte Activation

We describe a murine cDNA, designated Early T lymphocyte activation 1 (ETA-1) which is abundantly expressed after activation of T cells. Eta-1 encodes a highly acidic secreted product having structural features of proteins that bind to cellular adhesion receptors. The Eta-1 gene maps to a locus on murine chromosome 5 termed Ric that confers resistance to infection by Rickettsia tsutsugamushi (RT), an obligate intracellular bacterium that is the etiological agent for human scrub typhus. With one exception, inbred mouse strains that expressed the Eta-1a allele were resistant to RT infection (RicR), and inbred strains expressing the Eta-1b allele were susceptible (RicS). These findings suggest that Eta-1 is the gene inferred from previous studies of the Ric locus (5). Genetic resistance to RT infection is associated with a strong Eta-1 response in vivo and inhibition of early bacterial replication. Eta-1 gene expression appears to be part of a surprisingly rapid T cell-dependent response to bacterial infection that may precede classical forms of T cell-dependent immunity.

scholarly journals Systemic and Mucosal T-Lymphocyte Activation Induced by Recombinant Adenovirus Vaccines in Rhesus Monkeys

2009 ◽  
Vol 83 (20) ◽  
pp. 10596-10604 ◽  
Author(s):  
Yue Sun ◽  
Robert T. Bailer ◽  
Srinivas S. Rao ◽  
John R. Mascola ◽  
Gary J. Nabel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Rhesus Monkeys ◽  
Recombinant Adenovirus ◽  
Lymphocyte Activation ◽  
T Cell Responses ◽  
Cell Responses ◽  
T Lymphocyte Activation

ABSTRACT The administration of vectors designed to elicited cell-mediated immune responses may have other consequences that are clinically significant. To explore this possibility, we evaluated T-cell activation during the first 2 months after recombinant adenovirus serotype 5 (rAd5) prime or boost immunizations in rhesus monkeys. We also evaluated the kinetics of T-lymphocyte activation in both the systemic and the mucosal compartments after rAd5 administration in monkeys with preexisting immunity to Ad5. The rAd5 immunization induced lower-frequency Gag epitope-specific CD8+ T cells in the colonic mucosa than in the peripheral blood. There was evidence of an expansion of the simian immunodeficiency virus Gag-specific CD8+ T-cell responses, but not the Ad5 hexon-specific T-cell responses, following a homologous rAd5 boost. A striking but transient T-lymphocyte activation in both the systemic and the mucosal compartments of rhesus monkeys was observed after rAd5 immunization. These findings indicate that the administration of a vaccine vector such as Ad5 can induce a global activation of T cells.

scholarly journals Surfactant protein A inhibits T cell proliferation via its collagen-like tail and a 210-kDa receptor

1998 ◽  
Vol 275 (4) ◽  
pp. L679-L686 ◽  
Author(s):  
Paul Borron ◽  
Francis X. McCormack ◽  
Baher M. Elhalwagi ◽  
Zissis C. Chroneos ◽  
James F. Lewis ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
T Lymphocyte ◽  
Lymphocyte Proliferation ◽  
Pulmonary Surfactant ◽  
Protein A ◽  
T Cell Proliferation ◽  
T Lymphocyte Proliferation ◽  
Human T Lymphocyte

Investigation of possible mechanisms to describe the hyporesponsiveness of pulmonary leukocytes has led to the study of pulmonary surfactant and its constituents as immune suppressive agents. Pulmonary surfactant is a phospholipid-protein mixture that reduces surface tension in the lung and prevents collapse of the alveoli. The most abundant protein in this mixture is a hydrophilic molecule termed surfactant-associated protein A (SP-A). Previously, we showed that bovine (b) SP-A can inhibit human T lymphocyte proliferation and interleukin-2 production in vitro. Results presented in this investigation showed that different sources of human SP-A and bSP-A as well as recombinant rat SP-A inhibited human T lymphocyte proliferation in a dose-dependent manner. A structurally similar collagenous protein, C1q, did not block the in vitro inhibitory action of SP-A. The addition of large concentrations of mannan to SP-A-treated cultures also did not disrupt inhibition, suggesting that the effect is not mediated by the carbohydrate recognition domain of SP-A. Use of recombinant mutant SP-As revealed that a 36-amino acid Arg-Gly-Asp (RGD) motif-containing span of the collagen-like domain was responsible for the inhibition of T cell proliferation. A polyclonal antiserum directed against an SP-A receptor (SP-R210) completely blocked the inhibition of T cell proliferation by SP-A. These results emphasize a potential role for SP-A in dampening lymphocyte responses to exogenous stimuli. The data also provide further support for the concept that SP-A maintains a balance between the clearance of inhaled pathogens and protection against collateral immune-mediated damage.

scholarly journals Shikonin Suppresses Human T Lymphocyte Activation through Inhibition of IKKβActivity and JNK Phosphorylation

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ting Li ◽  
Fenggen Yan ◽  
Rui Wang ◽  
Hua Zhou ◽  
Liang Liu
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cell Activation ◽  
Nuclear Translocation ◽  
Lymphocyte Activation ◽  
Immunosuppressive Agent ◽  
Buffy Coat ◽  
T Lymphocyte Activation

The key role of T cells has been elaborated in mediating immune responses and pathogenesis of human inflammatory and autoimmune conditions. In the current study the effect of shikonin, a compound isolated from a medicinal plant, on inhibition of T-cell activation was firstly examined by using primary human T lymphocytes isolated from buffy coat. Results showed that shikonin dose dependently suppressed T-cell proliferation, IL-2 and IFN-γsecretion, CD69 and CD25 expression, as well as cell cycle arrest activated by costimulation of PMA/ionomycin or OKT-3/CD28 monoclonal antibodies. Moreover, these inhibitory responses mediated by shikonin were found to be associated with suppression of the NF-κB signaling pathway via inhibition of the IKKα/βphosphorylation, IκB-αphosphorylation and degradation, and NF-κB nuclear translocation by directly decreasing IKKβactivity. Moreover, shikonin suppressed JNK phosphorylation in the MAPKs pathway of T cells. In this connection, we conclude that shikonin could suppress T lymphocyte activation through suppressing IKKβactivity and JNK signaling, which suggests that shikonin is valuable for further investigation as a potential immunosuppressive agent.

scholarly journals Shockwaves increase T-cell proliferation and IL-2 expression through ATP release, P2X7 receptors, and FAK activation

2010 ◽  
Vol 298 (3) ◽  
pp. C457-C464 ◽  
Author(s):  
Tiecheng Yu ◽  
Wolfgang G. Junger ◽  
Changji Yuan ◽  
An Jin ◽  
Yi Zhao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
P38 Mapk ◽  
Cell Function ◽  
Receptor Activation ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
T Cell Proliferation ◽  
P2x7 Receptors ◽  
Mapk Activation

Shockwaves elicited by transient pressure disturbances are used to treat musculoskeletal disorders. Previous research has shown that shockwave treatment affects T-cell function, enhancing T-cell proliferation and IL-2 expression by activating p38 mitogen-activated protein kinase (MAPK) signaling. Here we investigated the signaling pathway by which shockwaves mediate p38 MAPK phosphorylation. We found that shockwaves at an intensity of 0.18 mJ/mm2induce the release of extracellular ATP from human Jurkat T-cells at least in part by affecting cell viability. ATP released into the extracellular space stimulates P2X7-type purinergic receptors that induce the activation of p38 MAPK and of focal adhesion kinase (FAK) by phosphorylation on residues Tyr397 and Tyr576/577. Elimination of released ATP with apyrase or inhibition of P2X7 receptors with the antagonists KN-62 or suramin significantly weakens FAK phosphorylation, p38 MAPK activation, IL-2 expression, and T-cell proliferation. Conversely, addition of exogenous ATP causes phosphorylation of FAK and p38 MAPK. Silencing of FAK expression also reduces these cell responses to shockwave treatment. We conclude that shockwaves enhance p38 MAPK activation, IL-2 expression, and T-cell proliferation via the release of cellular ATP and feedback mechanisms that involve P2X7 receptor activation and FAK phosphorylation.

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