Microglia induce myelin basic protein-specific T cell anergy or T cell activation, according to their state of activation

1999 ◽  
Vol 29 (10) ◽  
pp. 3063-3076 ◽  
Author(s):  
Malgosia K. Matyszak ◽  
Suzanne Denis-Donini ◽  
Stefania Citterio ◽  
Renato Longhi ◽  
Francesca Granucci ◽  
...  
Keyword(s):  
T Cell ◽  
Myelin Basic Protein ◽  
T Cell Activation ◽  
Cell Activation ◽  
Basic Protein ◽  
T Cell Anergy ◽  
Cell Anergy

scholarly journals Cyclo-oxygenase type 2-dependent prostaglandin E2 secretion is involved in retrovirus-induced T-cell dysfunction in mice

2004 ◽  
Vol 384 (3) ◽  
pp. 469-476 ◽  
Author(s):  
Souad RAHMOUNI ◽  
Einar Martin AANDAHL ◽  
Btissam NAYJIB ◽  
Mustapha ZEDDOU ◽  
Sandra GIANNINI ◽  
...  
Keyword(s):  
T Cell ◽  
Prostaglandin E2 ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphoproliferative Disease ◽  
Cell Dysfunction ◽  
T Cell Anergy ◽  
T Cell Dysfunction ◽  
Cell Anergy

MAIDS (murine AIDS) is caused by infection with the murine leukaemia retrovirus RadLV-Rs and is characterized by a severe immunodeficiency and T-cell anergy combined with a lymphoproliferative disease affecting both B- and T-cells. Hyperactivation of the cAMP-protein kinase A pathway is involved in the T-cell dysfunction of MAIDS and HIV by inhibiting T-cell activation through the T-cell receptor. In the present study, we show that MAIDS involves a strong and selective up-regulation of cyclo-oxygenase type 2 in the CD11b+ subpopulation of T- and B-cells of the lymph nodes, leading to increased levels of PGE2 (prostaglandin E2). PGE2 activates the cAMP pathway through G-protein-coupled receptors. Treatment with cyclo-oxygenase type 2 inhibitors reduces the level of PGE2 and thereby reverses the T-cell anergy, restores the T-cell immune function and ameliorates the lymphoproliferative disease.

scholarly journals PAG-Associated FynT Regulates Calcium Signaling and Promotes Anergy in T Lymphocytes

2007 ◽  
Vol 27 (5) ◽  
pp. 1960-1973 ◽  
Author(s):  
Dominique Davidson ◽  
Burkhart Schraven ◽  
André Veillette
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tyrosine Phosphorylation ◽  
T Cell Activation ◽  
Protein Tyrosine Kinase ◽  
Cell Activation ◽  
T Cell Anergy ◽  
Cell Anergy ◽  
Anergic T Cells ◽  
Selective Enhancement

ABSTRACT Phosphoprotein associated with glycolipid-enriched membranes (PAG), also named Csk-binding protein (Cbp), is a transmembrane adaptor associated with lipid rafts. It is phosphorylated on multiple tyrosines located in the cytoplasmic domain. One tyrosine, tyrosine 314 (Y314) in the mouse, interacts with Csk, a protein tyrosine kinase that negatively regulates Src kinases. This interaction enables PAG to inhibit T-cell antigen receptor (TCR)-mediated T-cell activation. PAG also associates with the Src-related kinase FynT. Genetic studies indicated that FynT was required for PAG tyrosine phosphorylation and binding of PAG to Csk in T cells. Herein, we investigated the function and regulation of PAG-associated FynT. Our data showed that PAG was constitutively associated with FynT in unstimulated T cells and that this association was rapidly lost in response to TCR stimulation. Dissociation of the PAG-FynT complex preceded PAG dephosphorylation and PAG-Csk dissociation after TCR engagement. Interestingly, in anergic T cells, the association of PAG with FynT, but not Csk, was increased. Analyses of PAG mutants provided evidence that PAG interacted with FynT by way of tyrosines other than Y314. Enforced expression of a PAG variant interacting with FynT, but not Csk, caused a selective enhancement of TCR-triggered calcium fluxes in normal T cells. Furthermore, it promoted T-cell anergy. Both effects were absent in mice lacking FynT, implying that the effects were mediated by PAG-associated FynT. Hence, besides enabling PAG tyrosine phosphorylation and the PAG-Csk interaction, PAG-associated FynT can stimulate calcium signals and favor T-cell anergy. These data improve our comprehension of the function of PAG in T cells. They also further implicate FynT in T-cell anergy.

scholarly journals T cell anergy in COVID-19 reflects virus persistence and poor outcomes

2020 ◽  
Author(s):  
Kerstin Renner ◽  
Christine Mueller ◽  
Charlotte Tiefenboeck ◽  
Jan-Niklas Salewski ◽  
Frederike Winter ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Severe Pneumonia ◽  
Cell Reactivity ◽  
Virus Persistence ◽  
T Cell Anergy ◽  
Cell Anergy ◽  
T Cell Reactivity ◽  
Poor Outcomes

Coronavirus disease 2019 (COVID-19) can lead to severe pneumonia and hyperinflammation. So far, insufficient or excessive T cell responses were described in patients. We applied novel approaches to analyze T cell reactivity and showed that T anergy is already present in non-ventilated COVID-19 patients, very pronounced in ventilated patients, strongly associated with virus persistence and reversible with clinical recovery. T cell activation was measured by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood and proved to be much more meaningful than classical readouts with PBMCs. Monocytes responded stronger in males than females and IL-2 partially reversed T cell anergy. Downstream markers of T cell anergy were also found in fresh blood samples of critically ill patients with severe T cell anergy. Based on our data we were able to develop a score to predict fatal outcomes and to identify patients that may benefit from strategies to overcome T cell anergy.

scholarly journals The T-cell anergy induced by Leishmania amazonensis antigens is related with defective antigen presentation and apoptosis

2004 ◽  
Vol 76 (3) ◽  
pp. 519-527 ◽  
Author(s):  
Roberta O. Pinheiro ◽  
Eduardo F. Pinto ◽  
Alessandra B. Benedito ◽  
Ulisses G. Lopes ◽  
Bartira Rossi-Bergmann
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Cell Activation ◽  
Leishmania Amazonensis ◽  
T Cell Anergy ◽  
Crude Antigen ◽  
Lymph Node Cells ◽  
Cell Anergy

Leishmania amazonensis is the main agent of diffuse cutaneous leishmaniasis, a disease associated with anergic immune responses. In this study we show that the crude antigen of Leishmania amazonensis (LaAg) but not L. braziliensis promastigotes (LbAg) contains substances that suppress mitogenic and spontaneous proliferative responses of T cells. The suppressive substances in LaAg are thermoresistant (100ºC/1h) and partially dependent on protease activity. T cell anergy was not due to a decreased production of growth factors as it was not reverted by addition of exogenous IL-2, IL-4, IFN-gamma or IL-12. LaAg did not inhibit anti-CD3-induced T cell activation, suggesting that anergy was due to a defect in antigen presentation. It was also not due to cell necrosis, but was accompanied by expressive DNA fragmentation in lymph node cells, indicative of apoptosis. Although pre-incubation of macrophages with LaAg prevented their capacity to present antigens, this effect was not due to apoptosis of the former. These results suggest that the T cell anergy found in diffuse leishmaniasis may be the result of parasite antigen-driven apoptosis of those cells following defective antigen presentation.

scholarly journals Thymic T cell anergy in autoimmune nonobese diabetic mice is mediated by deficient T cell receptor regulation of the pathway of p21ras activation.

1993 ◽  
Vol 177 (4) ◽  
pp. 1221-1226 ◽  
Author(s):  
M J Rapoport ◽  
A H Lazarus ◽  
A Jaramillo ◽  
E Speck ◽  
T L Delovitch
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tyrosine Phosphorylation ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Receptor ◽  
T Cell Anergy ◽  
Nonobese Diabetic ◽  
Cell Anergy

Thymic T cell anergy, as manifested by thymocyte proliferative unresponsiveness to antigens expressed in the thymic environment, is commonly believed to mediate the acquisition of immunological self-tolerance. However, we previously found that thymic T cell anergy may lead to the breakdown of tolerance and predispose to autoimmunity in nonobese diabetic (NOD) mice. Here, we show that NOD thymic T cell anergy, as revealed by proliferative unresponsiveness in vitro after stimulation through the T cell receptor (TCR), is associated with defective TCR-mediated signal transduction along the PKC/p21ras/p42mapk pathway of T cell activation. PKC activity is reduced in NOD thymocytes. Activation of p21ras is deficient in quiescent and stimulated NOD T cells, and this is correlated with a significant reduction in the tyrosine phosphorylation of p42mapk, a serine/threonine kinase active downstream of p21ras. Treatment of NOD T cells with a phorbol ester not only enhances their p21ras activity and p42mapk tyrosine phosphorylation but also restores their proliferative responsiveness. Since p42mapk activity is required for progression through to S phase of the cell cycle, our data suggest that reduced tyrosine phosphorylation of p42mapk in stimulated NOD T cells may abrogate its activity and elicit the proliferative unresponsiveness of these cells.

scholarly journals T cell anergy in COVID-19 reflects virus persistence and poor outcomes

2020 ◽  
Author(s):  
Kerstin Renner ◽  
Christine Müller ◽  
Charlotte Tiefenböck ◽  
Jan-Niklas Salewski ◽  
Frederike Winter ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Severe Pneumonia ◽  
Cell Reactivity ◽  
Virus Persistence ◽  
T Cell Anergy ◽  
Cell Anergy ◽  
T Cell Reactivity ◽  
Poor Outcomes

Abstract Coronavirus disease 2019 (COVID-19) can lead to severe pneumonia and hyperinflammation. So far, insufficient or excessive T cell responses were described in patients. We applied novel approaches to analyze T cell reactivity and showed that T anergy is already present in non-ventilated COVID-19 patients, very pronounced in ventilated patients, strongly associated with virus persistence and reversible with clinical recovery. T cell activation was measured by downstream effects on responder cells like basophils, plasmacytoid dendritic cells, monocytes and neutrophils in whole blood and proved to be much more meaningful than classical readouts with PBMCs. Monocytes responded stronger in males than females and IL-2 partially reversed T cell anergy. Downstream markers of T cell anergy were also found in fresh blood samples of critically ill patients with severe T cell anergy. Based on our data we were able to develop a score to predict fatal outcomes and to identify patients that may benefit from strategies to overcome T cell anergy.

303. Further characterisation of lymphocyte-suppressing activity in gonadal fluids

2005 ◽  
Vol 17 (9) ◽  
pp. 129
Author(s):  
M. Crane ◽  
L. Foulds ◽  
J. Muir ◽  
D. Aridi ◽  
P. Hutchinson ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Transplant Rejection ◽  
Calf Serum ◽  
Autoimmune Response ◽  
T Cell Anergy ◽  
Activation Assay ◽  
Proliferation In Vitro

Protection of the developing gametes from an autoimmune response within the testis and ovary is essential for reproductive success, and autoimmune infertility represents a failure of this protection. The gonads also represent favorable sites for grafts of foreign tissue, that is, they are ‘immunologically privileged’. The actual mechanisms responsible for testicular and ovarian immune privilege are poorly understood. However, it has been well established that testicular interstitial fluid and ovarian fluid have profound inhibitory effects on T-cell activation and proliferation in vitro. We have established previously that a partially purified preparation of the inhibitor, isolated from bovine follicular fluid, suppresses proliferation in an in vitro T-cell activation assay, through induction of T-cell anergy and/or atypical apoptosis. Addition of increasing doses of normal fetal calf serum and/or bovine serum albumin blocks the actions of the inhibitor and progressively increases the ED50 of the assay. It has also been shown that stimulating the T-cells with phorbol-12-myristate-13-acetate (PMA) in place of a polyclonal mitogenic stimulus such as phytohaemagglutinin bypasses the anergic effects of the inhibitor. These results suggest that the activity of the inhibitor may be negatively regulated in the circulation and tissues by serum-derived proteins and other factors. These data also indicate that the inhibitor’s activity is mediated through a specific cellular pathway, most likely involving protein kinase C isotypes, which are activated by PMA. Further work will delineate the molecular pathways and mechanisms of serum regulation of the gonadal lymphocyte-suppressing activity, which may be exploited in the treatment of autoimmune diseases and for prevention of transplant rejection.

scholarly journals T–cell anergy and peripheral T–cell tolerance

2001 ◽  
Vol 356 (1409) ◽  
pp. 625-637 ◽  
Author(s):  
Robert Lechler ◽  
Jian-Guo Chai ◽  
Federica Marelli-Berg ◽  
Giovanna Lombardi
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Contact ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
T Cell Anergy ◽  
Cell Anergy ◽  
Anergic T Cells

The discovery that T–cell recognition of antigen can have distinct outcomes has advanced understanding of peripheral T–cell tolerance, and opened up new possibilities in immunotherapy. Anergy is one such outcome, and results from partial T–cell activation. This can arise either due to subtle alteration of the antigen, leading to a lower–affinity cognate interaction, or due to a lack of adequate co–stimulation. The signalling defects in anergic T cells are partially defined, and suggest that T–cell receptor (TCR) proximal, as well as downstream defects negatively regulate the anergic T cell's ability to be activated. Most importantly, the use of TCR–transgenic mice has provided compelling evidence that anergy is an in vivo phenomenon, and not merely an in vitro artefact. These findings raise the question as to whether anergic T cells have any biological function. Studies in rodents and in man suggest that anergic T cells acquire regulatory properties; the regulatory effects of anergic T cells require cell to cell contact, and appear to be mediated by inhibition of antigen–presenting cell immunogenicity. Close similarities exist between anergic T cells, and the recently defined CD4 + CD25 + population of spontaneously arising regulatory cells that serve to inhibit autoimmunity in mice. Taken together, these findings suggest that a spectrum of regulatory T cells exists. At one end of the spectrum are cells, such as anergic and CD4 + CD25 + T cells, which regulate via cell–to–cell contact. At the other end of the spectrum are cells which secrete antiinflammatory cytokines such as interleukin 10 and transforming growth factor–β. The challenge is to devise strategies that reliably induce T–cell anergy in vivo , as a means of inhibiting immunity to allo– and autoantigens.

Sign in / Sign up

Export Citation Format

Share Document