scholarly journals Increased Expressions of OX40 and OX40 Ligand in Patients with Primary Immune Thrombocytopenia

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Dawei Cui ◽  
Yan Lv ◽  
Xinwang Yuan ◽  
Guoxiang Ruan ◽  
Yu Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Thrombocytopenia ◽  
Solid Phase ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Autoimmune Disorder ◽  
Expression Levels ◽  
Platelet Counts ◽  
Ox40 Ligand ◽  
Necrosis Factor

Background. OX40, which is also known as tumor necrosis factor receptor superfamily member 4 (TNFRSF4), and its ligand (OX40L) play a critical role in the pathogenesis of autoimmune diseases. Immune thrombocytopenia (ITP), a hemorrhagic autoimmune disorder, is characterized by low platelet counts that are predominantly caused by antiplatelet autoantibodies. In this study, we firstly investigated the clinical significance of OX40 and OX40L expression in the pathogenesis of ITP in patients. Methods. Fifty-four newly diagnosed ITP patients and 24 healthy controls (HCs) were enrolled in this study. The percentage of OX40+CD4+T cells among CD4+T cells was analyzed by flow cytometry, and the expression levels of OX40 and OX40L mRNA were analyzed by quantitative real-time PCR. Plasma soluble OX40L (sOX40L) levels were analyzed by ELISA, and plasma levels of antiplatelet autoantibodies were analyzed by a solid-phase technique. Results. Compared with HCs, the frequencies of OX40+CD4+T cells were significantly increased in ITP patients, particularly in patients with positive antiplatelet autoantibodies compared to those with negative antiplatelet autoantibodies. The elevated frequencies of OX40+CD4+T cells were negatively correlated with low platelet counts in patients with positive antiplatelet autoantibodies. Plasma sOX40L levels in ITP patients were significantly greater than those in HCs and increased in patients with positive antiplatelet autoantibodies compared to those with negative antiplatelet autoantibodies. Plasma sOX40L levels were negatively correlated with low platelet counts in patients with positive antiplatelet autoantibodies. Additionally, the mRNA expression levels of OX40 and OX40L in PBMCs from ITP patients were also notably greater than those from HCs, and the expression levels of OX40 and OX40L were significantly different in ITP patients with positive and negative antiplatelet autoantibodies. Conclusion. These data indicated that increased expression levels of OX40 and OX40L were involved in the pathogenesis of ITP, and OX40 and OX40L may be valuable therapeutic targets for ITP.

scholarly journals Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Trine B. Levring ◽  
Martin Kongsbak-Wismann ◽  
Anna K. O. Rode ◽  
Fatima A. H. Al-Jaberi ◽  
Daniel V. Lopez ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Glucose Uptake ◽  
Tumor Necrosis ◽  
Gradient Centrifugation ◽  
Tumor Necrosis Factor Receptor ◽  
Down Regulation ◽  
Interacting Protein ◽  
Human T Cells ◽  
Necrosis Factor

Abstract In addition to antigen-driven signals, T cells need co-stimulatory signals for robust activation. Several receptors, including members of the tumor necrosis factor receptor superfamily (TNFRSF), can deliver co-stimulatory signals to T cells. Thioredoxin interacting protein (TXNIP) is an important inhibitor of glucose uptake and cell proliferation, but it is unknown how TXNIP is regulated in T cells. The aim of this study was to determine expression levels and regulation of TXNIP in human T cells. We found that naïve T cells express high levels of TXNIP and that treatment of blood samples with TNF results in rapid down-regulation of TXNIP in the T cells. TNF-induced TXNIP down-regulation correlated with increased glucose uptake. Furthermore, we found that density gradient centrifugation (DGC) induced down-regulation of TXNIP. We demonstrate that DGC induced TNF production that paralleled the TXNIP down-regulation. Treatment of blood with toll-like receptor (TLR) ligands induced TNF production and TXNIP down-regulation, suggesting that damage-associated molecular patterns (DAMPs), such as endogenous TLR ligands, released during DGC play a role in DGC-induced TXNIP down-regulation. Finally, we demonstrate that TNF-induced TXNIP down-regulation is dependent on caspase activity and is caused by caspase-mediated cleavage of TXNIP.

scholarly journals Critical role of tumor necrosis factor receptor 1 in the pathogenesis of pulmonary emphysema in mice

2016 ◽  
Vol Volume 11 ◽  
pp. 1705-1712 ◽  
Author(s):  
Masaki Fujita ◽  
Ouchi Hiroshi ◽  
Satoshi Ikemage ◽  
Eiji Harada ◽  
Takemasa Matsumoto ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Pulmonary Emphysema ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Necrosis Factor

Glucocorticoid-induced tumor necrosis factor receptor–related protein co-stimulation facilitates tumor regression by inducing IL-9–producing helper T cells

2015 ◽  
Vol 21 (9) ◽  
pp. 1010-1017 ◽  
Author(s):  
Il-Kyu Kim ◽  
Byung-Seok Kim ◽  
Choong-Hyun Koh ◽  
Jae-Won Seok ◽  
Jun-Seok Park ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Regression ◽  
Tumor Necrosis Factor Receptor ◽  
Helper T Cells ◽  
Related Protein ◽  
Necrosis Factor

scholarly journals A Critical Role of the p75 Tumor Necrosis Factor Receptor (p75TNF-R) in Organ Inflammation Independent of  TNF, Lymphotoxin α, or the p55TNF-R

1998 ◽  
Vol 188 (7) ◽  
pp. 1343-1352 ◽  
Author(s):  
Eleni Douni ◽  
George Kollias
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Peripheral Blood Mononuclear ◽  
Enhanced Production ◽  
Wide Range ◽  
Lymphotoxin Α ◽  
Necrosis Factor

Despite overwhelming evidence that enhanced production of the p75 tumor necrosis factor receptor (p75TNF-R) accompanies development of specific human inflammatory pathologies such as multi-organ failure during sepsis, inflammatory liver disease, pancreatitis, respiratory distress syndrome, or AIDS, the function of this receptor remains poorly defined in vivo. We show here that at levels relevant to human disease, production of the human p75TNF-R in transgenic mice results in a severe inflammatory syndrome involving mainly the pancreas, liver, kidney, and lung, and characterized by constitutively increased NF-κB activity in the peripheral blood mononuclear cell compartment. This process is shown to evolve independently of the presence of TNF, lymphotoxin α, or the p55TNF-R, although coexpression of a human TNF transgene accelerated pathology. These results establish an independent role for enhanced p75TNF-R production in the pathogenesis of inflammatory disease and implicate the direct involvement of this receptor in a wide range of human inflammatory pathologies.

Ligation of CD137 receptor prevents and reverses established anergy of CD8+ cytolytic T lymphocytes in vivo

Blood ◽  
2004 ◽  
Vol 103 (1) ◽  
pp. 177-184 ◽  
Author(s):  
Ryan A. Wilcox ◽  
Koji Tamada ◽  
Dallas B. Flies ◽  
Gefeng Zhu ◽  
Andrei I. Chapoval ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Molecular Mechanisms ◽  
Transplant Rejection ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
T Cell Anergy ◽  
Cell Anergy ◽  
Induced Tolerance

Abstract T-cell anergy is a tolerance mechanism defined as a hyporesponsive status of antigen-specific T cells upon prior antigen encounter and is believed to play a critical role in the evasion of tumor immunity and the amelioration of allogeneic transplant rejection. Molecular mechanisms in controlling T-cell anergy are less known. We show here that administration of an agonistic monoclonal antibody (mAb) to CD137, a member of the tumor necrosis factor receptor superfamily, prevents the induction of CD8+ cytolytic T-lymphocyte (CTL) anergy by soluble antigens. More importantly, CD137 mAb restores the functions of established anergic CTLs upon reencountering their cognate antigen. As a result, infusion of CD137 mAb inhibits progressive tumor growth that is caused by soluble tumor antigen-induced tolerance in a P815R model. CD137 mAb also restores proliferation and effector functions of anergic alloreactive 2C T cells in a bone marrow transplantation model. Our results indicate that ligation of CD137 receptor delivers a regulatory signal for T-cell anergy and implicate manipulation of the CD137 pathway as a new approach to break T-cell tolerance.

scholarly journals The Significance of Tumor Necrosis Factor Receptor Type II in CD8+ Regulatory T Cells and CD8+ Effector T Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Lin-Lin Ye ◽  
Xiao-Shan Wei ◽  
Min Zhang ◽  
Yi-Ran Niu ◽  
Qiong Zhou
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Regulatory T Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Effector T Cells ◽  
Receptor Type ◽  
Type Ii ◽  
Necrosis Factor

scholarly journals SHIP limits immunoregulatory capacity in the T-cell compartment

Blood ◽  
2009 ◽  
Vol 113 (13) ◽  
pp. 2934-2944 ◽  
Author(s):  
Michelle M. Collazo ◽  
Daniela Wood ◽  
Kim H. T. Paraiso ◽  
Erin Lund ◽  
Robert W. Engelman ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Necrosis Factor Receptor ◽  
Sh2 Domain ◽  
Graft Versus Host ◽  
Histocompatibility Complex ◽  
Delayed Rejection ◽  
Organ Graft ◽  
Necrosis Factor

Abstract Regulatory T cells (Tregs) play a pivotal role in preventing autoimmunity, graft-versus-host disease (GVHD), and organ graft rejection. We previously showed that either germline or induced SH2 domain–containing inositol 5-phosphatase (SHIP) deficiency in the host abrogates GVHD. Here we show that SHIP deficiency promotes an increase of CD4+CD25+FoxP3+ Tregs and CD4+CD25−FoxP3+“naive” T cells in the periphery that display increased CD103, glucocorticoid-induced tumor necrosis factor receptor–related protein (GITR), OX40, and FcγRII/III expression. SHIP deficiency does not compromise Treg function because SHIP-deficient CD3+CD4+CD25+ Tregs are as suppressive as wild-type (WT) CD3+CD4+CD25+ Treg. Interestingly, like conventional Tregs, SHIP−/− CD4+CD25− T cells are unresponsive to major histocompatibility complex (MHC)–mismatched stimulators and suppress allogeneic responses by T cells in vitro. In addition, SHIP−/− CD4+CD25− T cells mediate reduced lethal GVHD on adoptive transfer to MHC-mismatched hosts. Furthermore, hosts with induced SHIP deficiency exhibit delayed rejection of MHC-mismatched cardiac grafts. Thus, SHIP is required for robust graft-versus-host and host-versus-graft responses by CD4+ T cell and limits their immunoregulatory capacity. These findings further define the immunosuppressive mechanisms that result from SHIP deficiency and provide additional justification for targeting SHIP in clinical transplantation.

Immune Thrombocytopenia Associated to Low-Dose Alemtuzumab Therapy in Chronic Lymphocytic Leukemia: A Single Retrospective Center Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4598-4598
Author(s):  
Gianluigi Reda ◽  
Francesco Maura ◽  
Giuseppe Gritti ◽  
Daniele Vincenti ◽  
Mariarita Sciumé ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Disease Progression ◽  
Cumulative Dose ◽  
Immune Thrombocytopenia ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
Autoimmune Disorder ◽  
Intravenous Immunoglobulins ◽  
Lymphocytic Leukemia ◽  
Platelet Counts

Abstract Abstract 4598 Immune thrombocytopenia (ITP) is a common autoimmune complication in chronic lymphocytic leukemia (CLL), occurring in up to 5% of patients. The occurrence of alemtuzumab-associated ITP have been rarely reported in CLL and it has never been reported so far as a significant event complicating alemtuzumab treatment in clinical trials. Recently, a new distinctive form of secondary ITP occurring in 6 out of 215 patients with relapsing-remitting multiple sclerosis treated with alemtuzumab in a randomized, controlled phase II trial has been reported (Cuker et al, Blood 2011). We investigated the incidence of ITP in a cohort of 64 consecutive patients treated with low-dose alemtuzumab for relapsed/refractory CLL from 2003 to 2010. Subcutaneous alemtuzumab was administered at the dose of 10 mg three times a week, up to 18 weeks. ITP was documented in 12/64 patients: in 3 patients (4.7%) ITP developed before alemtuzumab treatment and no relapses of the autoimmune disorder were observed during the treatment; in 9 patients (14.8%, with an incidence of 5.7 events/100 patient-year) ITP developed after alemtuzumab treatment. Median time to ITP from initial alemtuzumab exposure was 12 months (range 1–42 months). Concomitant hemolytic anemia (Evans syndrome) was observed in one patient. At ITP onset, median platelet counts were 11×109/L (range 3–70) and anti-platelet antibodies (Capture P® Method, ImmucorGamma, Norcross GA, USA) were found in 7 of the 8 patients tested. No patients showed severe or life-threatening bleeding. Three of nine patients who developed ITP after alemtuzumab therapy, experienced CLL progression requiring chemo-immunotherapy after 3, 4 and 13 months from ITP onset, respectively. One patient achieved a partial remission of CLL with ITP resolution, while the other two died of disease progression. In the remaining six cases, ITP was not associated with disease progression and was treated with corticosteroids and/or intravenous immunoglobulins. Five patients achieved normal platelet counts, while one patient did not respond. Low-dose alemtuzumab (theoretical cumulative dose 540 mg, equal to half of the classic cumulative dose and one-third of the individual dose) is an effective, safe and well tolerated treatment for CLL, as reported by several recent studies (Cortelezzi et al, Leukemia 2009; Brit J Haematol 2011). In our cohort of CLL patients treated with alemtuzumab, the incidence of ITP was 14.8% that is almost three times higher than previously reported in CLL. These data may indicate a role of T-lymphocyte dysregulation induced by alemtuzumab in the pathogenesis of ITP. Our data also suggested the importance of monitoring platelet counts during follow-up in patients treated with low-dose alemtuzumab for both haematological and non-haematological diseases. Disclosures: No relevant conflicts of interest to declare.

Tumor Necrosis Factor Receptor Expression in HIV-1-Infected CD4+ T Cells

1994 ◽  
Vol 38 (12) ◽  
pp. 1005-1008 ◽  
Author(s):  
Didier Hober ◽  
Donat de Groote ◽  
Nathalie Vanpouille ◽  
Isabelle Dehart ◽  
Lu Shen ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Necrosis Factor ◽  
Cd4 T Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Receptor Expression ◽  
Hiv 1 ◽  
Necrosis Factor
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