Search results for "CD28"
showing 10 items of 70 documents
Minimal hepatic encephalopathy is associated with expansion and activation of CD4+CD28−, Th22 and Tfh and B lymphocytes
2017
AbstractPeripheral inflammation acts synergistically with hyperammonemia in inducing neurological alterations in cirrhotic patients with minimal hepatic encephalopathy (MHE). We hypothesized that appearance of MHE would be associated to some specific qualitative change in peripheral inflammation. The aim of this work was to characterize the changes in peripheral inflammation associated to appearance of MHE. We analyzed it by immunophenotyping and cytokine profile analysis, in cirrhotic patients without or with MHE and controls. The main alterations associated specifically with MHE are: 1) increased activation of all subtypes of CD4+ T-lymphocytes, with the increased expression of CD69; 2) i…
CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes
2003
Azathioprine and its metabolite 6-mercaptopurine (6-MP) are immunosuppressive drugs that are used in organ transplantation and autoimmune and chronic inflammatory diseases such as Crohn disease. However, their molecular mechanism of action is unknown. In the present study, we have identified a unique and unexpected role for azathioprine and its metabolites in the control of T cell apoptosis by modulation of Rac1 activation upon CD28 costimulation. We found that azathioprine and its metabolites induced apoptosis of T cells from patients with Crohn disease and control patients. Apoptosis induction required costimulation with CD28 and was mediated by specific block- ade of Rac1 activation thro…
Association of T-cell regulatory gene polymorphisms with oral squamous cell carcinoma
2010
Costimulatory molecules have complementary effects on T-cell activation and their balance may control the development of oral cancer. The aim of this study was to determine the relevance of cytotoxic T-lymphocyte antigen 4 (CTLA-4), CD28 and inducible costimulator (ICOS) polymorphisms in oral squamous cell carcinoma (OSCC). Genotyping for CTLA-4 (-1661 A/G and +49 A/G), CD28 (0 C/G and +3160 G/T) and ICOS (+637 A/C and +1599 C/T) was performed in the 83 patients with OSCC, compared to the 40 unrelated healthy volunteers as controls. The genotype CTLA-4 -1661 was significantly different between the patient group and the control group. The allele CTLA-4 -1661 G was significantly found more fr…
Interruption of CD28-mediated costimulation during allergen challenge protects mice from allergic airway disease
2012
Background Allergic asthma is a T H 2-promoted hyperreactivity with an immediate, IgE, and mast cell–dependent response followed by eosinophil-dominated inflammation and airway obstruction. Objective Because costimulation by CD28 is essential for T H 2 but not T H 1 responses, we investigated the effect of selective interference with this pathway in mice using the models of ovalbumin and house dust mite–induced airway inflammation. Methods To study the role of CD28 in the effector phase of allergic airway inflammation, we developed an inducibly CD28-deleting mouse strain or alternatively used a CD28 ligand-binding site–specific mouse anti-mouse mAb blocking CD28 engagement. Results We show …
Stimulation of human T cells by microbial 'superantigens'.
1991
The enterotoxins and the TSST of S. aureus, the erythrogenic toxins A and C of S. pyogenes and a still uncharacterized exoprotein of M. arthritidis belong to a family of exotoxins that have in common a potent mitogenic activity for T lymphocytes of several species. These proteins stimulate CD4+ and C8+ T cells, as well as a fraction of gamma delta TCR-bearing T cells by cross-linking variable parts of the T cell antigen receptor with MHC class II molecules on accessory or target cells. They are functionally bivalent molecules having distinct interaction sites for variable parts of the TCR and for nonpolymorphic parts of the MHC class II molecule. For alpha beta TCR-bearing T cells the V bet…
Mycobacterial antigen(s) induce anergy by altering TCR- and TCR/CD28-induced signalling events: insights into T-cell unresponsiveness in leprosy.
2009
Present study investigates the role of Mycobacterium leprae (M. leprae) antigens on TCR- and TCR/CD28-induced signalling leading to T-cell activation and further correlates these early biochemical events with T-cell anergy, as prevailed in advanced stages of leprosy. We observed that both whole cell lystae (WCL) and soluble fraction of M. leprae sonicate (MLSA) not only inhibited TCR, thapsigargin and ionomycin induced calcium fluxes by diminishing the opening of calcium channels, but also TCR- or TCR/CD28-induced proximal signalling events like phosphorylation of Zap-70 and protein kinase-C (PKC) activity. Study of TCR- and TCR/CD28-induced downstream signals revealed that M. leprae antige…
Stimulator cell-dependent requirement for CD2- and LFA-1-mediated adhesions in T lymphocyte activation by superantigenic toxins.
1992
Abstract The staphylococcal enterotoxins and related microbial T cell mitogens stimulate T cells by cross-linking variable parts of the T cell receptor (TCR) with MHC class II molecules on accessory or target cells. We have used cloned human T cells and defined tumor cells as accessory cells (AC) to study the requirements for T cell activation by these toxins. On AC expressing high levels of CD54 (intercellular adhesion molecule-1, ICAM-1) and CD58 (lymphocyte function-associated antigen-3, LFA-3), mAb to CD2 were relatively ineffective in inhibiting the response to the toxins and antibodies to the lymphocyte function-associated antigen-1 (LFA-1) did not inhibit at all. If added together, h…
An antigen-independent physiological activation pathway for L3T4+ T lymphocytes.
1987
The data presented in this report describe an antigen-independent activation pathway leading to reinduction of proliferation of class II major histocompatibility complex (MHC)-restricted murine T cell lines that after previous antigen-specific stimulation reverted to a resting state. Antigen-independent proliferation and interleukin 2 (IL2)-receptor expression occur in the presence of splenic accessory cells, exogenous IL2 and a soluble factor(s) provisionally termed T cell-stimulating factor(s) (TSF). Each of these components is essential for inducing growth. TSF is found in the supernatant of an autoreactive T cell line upon stimulation with syngeneic accessory cells. Neither TSF nor acce…
T cell activation defect in hemodialysis patients: Evidence for a role of the B7/CD28 pathway
1993
T cell activation defect in hemodialysis patients: Evidence for a role of the B7/CD28 pathway. The immunosuppressive effect of chronic renal failure is correlated with an impaired proliferation of peripheral blood leukocytes in vitro . This is mainly due to an impaired function of the accessory cells rather than the T cells. Here we tried to define a missing accessory signal for T cell activation in hemodialysis patients. We substituted cell surface bound molecules by adding tumor cell lines to the in vitro assays that express different patterns of accessory molecules. Cell lines that express the costimulatory B7 molecule reconstituted the activation of patients' cells whereas B7 negative c…
Defective T cell receptor/CD3 complex signaling in human type I diabetes
1994
The autoimmune process leading to the destruction of pancreatic β-cells is mediated by T lymphocytes. Peripheral T cells from subjects with preclinical and clinical type I diabetes respond weakly in vitro to lectin stimulation. We, therefore, investigated in a group of newly diagnosed diabetic patients the presence of a defect in the signal transduction pathway of the T cell receptor (TcR)/CD3 complex. Following stimulation with anti-CD3-coupled beads, the proliferative response in diabetic T cells was significantly decreased in comparison with that from normal T cells. Interestingly, addition of either recombinant interleukin (IL)-2 or phorbol 12-myristate 13-acetate to the cell culture wa…