Search results for "CD4 antigen"
showing 10 items of 45 documents
Components of an antigen-/T cell receptor-independent pathway of lymphokine production
1991
The general way to induce the synthesis of lymphokines by T cells is the stimulation through the T cell receptor (TcR) complex which results in an increase of intracellular [Ca2+] and in the activation of a tyrosine kinase as well as of protein kinase C. Lymphokine production induced via the TcR is inhibited by the immunosuppressive drug cyclosporin A (CsA). However, an alternative pathway of lymphokine production exists. Several T lymphocyte clones can synthesize interferon-gamma (IFN-gamma), granulocyte-monocyte colony-stimulating factor, and small amounts of interleukin (IL3) when stimulated with syngeneic or allogeneic accessory cells (AC) plus IL2. In contrast to the TcR pathway the al…
Altered intracellular sorting signals do not influence the efficacy of genetic melanoma vaccines incorporating helper determinants in mice.
2004
Background A genetic melanoma vaccine consisting of cDNA encoding the model self-antigen tyrosinase-related protein 2 (TRP2) fused in-frame to the immunogenic enhanced green fluorescent protein (EGFP) was able to break immune tolerance and stimulate CD8+ T cells in vivo. In the present study we investigated whether alteration of the intracellular antigen localization as a result of the linkage with immune-enhancing helper proteins affects the resulting immune response. Methods Expression plasmids and recombinant adenoviruses were constructed encoding various fusion proteins with different intracellular sorting signals which direct the antigen to the cytosol, the endoplasmic reticulum or the…
Reduced CD4 and CD8 expression in human thymuses treated with soluble CD4.
1991
Recent data suggest that accessory molecules like CD4 and CD8 act as co-receptors in intrathymic T-cell development. Soluble CD4 (sCD4) molecules offer a novel experimental approach to investigate the relevance of CD4 interaction with its putative intrathymic receptor for T-cell maturation. We attempted to inhibit binding of surface CD4 on thymocytes to its intrathymic receptor competitively by introduction of human sCD4 into human thymus tissue cultures. Our results demonstrate that sCD4, while not affecting peripheral T-cell responses as shown in control experiments, significantly affects intrathymic development of T lymphocytes. Immature CD4CD8 double positive (DP) thymocytes responded w…
Modifications of general parameters of immune activation in the sera of Sicilian patients with Boutonneuse fever
1998
SUMMARYThe serum levels of β2-microglobulin (β2-M), soluble HLA class I antigen (sHLA-I), soluble CD4 (sCD4) and CD8 (sCD8) were studied in 98 Sicilian patients with Boutonneuse fever (BF). In different stages of infection all markers were significantly increased in sera from Sicilian patients with acute BF compared with healthy controls. sCD8 and sHLA-I reached the peak in the second week after the onset of symptoms, whereas sCD4 and β2-M reached the peak in the first week. Afterwards sCD8 decreased to the levels of controls within the third week, the other parameters decreased later and were unmodified until the third week of infection. Significant correlations were found between sCD4 and…
Elevated Regulatory T Cell Levels in Glaucoma Patients in Comparison to Healthy Controls.
2016
Many studies analyzing neurodegenerative diseases demonstrate altered frequencies of regulatory T cells (Tregs). Till date, there is hardly any information concerning Tregs in glaucoma. To gather first results concerning Treg levels in glaucoma patients, we aimed to investigate whether the number of CD4(+)CD25(+)T cells vary in the patients suffering from primary open-angle glaucoma (POAG) and healthy controls.Heparinized blood samples were collected from 16 healthy individuals and 16 POAG patients. The groups were age and gender matched. A density gradient centrifugation over Ficoll-Paque was performed to isolate the peripheral blood mononuclear cells. The resulting cells were stained with…
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…
Defective expression of CD95 (FAS/APO-1) molecule suggests apoptosis impairment of T and B cells in HLA-B8, DR3-positive individuals.
1997
Activation-induced apoptosis is one of the primary control mechanisms for the negative selection of an immune response, leading to maintenance of immune homeostasis and selective T cell deletion. The interaction between the surface molecule Fas and its ligand (FasL) has been proposed as a primary mechanism initiating T cell apoptosis. The T cell receptor modulates the expression and function of these molecules. Defects in the Fas/FasL apoptosis pathway have been shown to result in autoimmune disease in humans and in murine models. Because subjects carrying the HLA-B8, DR3 haplotype show a number of immune dysfunctions, including membrano-proliferative glomerulonephritis, systemic lupus eryt…
Activated glycoprotein A repetitions predominant (GARP)-expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized m…
2015
Background Recently, we developed a humanized mouse model of allergen-induced IgE-dependent gut inflammation in PBMC-engrafted immunodeficient mice. Objective In the present study, we wanted to investigate the role of regulatory T (Treg) cells and their activation status in this model. Methods Nonobese diabetic-severe combined immunodeficiency-γc −/− mice were injected intraperitoneally with human PBMCs from allergic donors together with the respective allergen or NaCl as control in the presence or absence of different concentrations of CD4 + CD25 + Treg cells of the same donor. After an additional allergen boost 1 week later, mice were challenged with the allergen rectally on day 21 and gu…
Protection from graft-versus-host disease by HIV-1 envelope protein gp120-mediated activation of human CD4+CD25+ regulatory T cells.
2009
AbstractNaturally occurring CD4+CD25+ regulatory T cells (Tregs) represent a unique T-cell lineage that is endowed with the ability to actively suppress immune responses. Therefore, approaches to modulate Treg function in vivo could provide ways to enhance or reduce immune responses and lead to novel therapies. Here we show that the CD4 binding human immunodeficiency virus-1 envelope glycoprotein gp120 is a useful and potent tool for functional activation of human Tregs in vitro and in vivo. Gp120 activates human Tregs by binding and signaling through CD4. Upon stimulation with gp120, human Tregs accumulate cyclic adenosine monophosphate (cAMP) in their cytosol. Inhibition of endogeneous cA…
A specific CD4 epitope bound by tregalizumab mediates activation of regulatory T cells by a unique signaling pathway
2014
CD4(+)CD25(+) regulatory T cells (Tregs) represent a specialized subpopulation of T cells, which are essential for maintaining peripheral tolerance and preventing autoimmunity. The immunomodulatory effects of Tregs depend on their activation status. Here we show that, in contrast to conventional anti-CD4 monoclonal antibodies (mAbs), the humanized CD4-specific monoclonal antibody tregalizumab (BT-061) is able to selectively activate the suppressive properties of Tregs in vitro. BT-061 activates Tregs by binding to CD4 and activation of signaling downstream pathways. The specific functionality of BT-061 may be explained by the recognition of a unique, conformational epitope on domain 2 of th…