Search results for "ZAP70"

NKG2D stimulation of CD8(+) T cells during priming promotes their capacity to produce cytokines in response to viral infection in mice

2017

NKG2D is an activating receptor that is expressed on most cytotoxic cells of the immune system, including NK cells, γδ and CD8+ T cells. It is still a matter of debate whether and how NKG2D mediates priming of CD8+ T cells in vivo, due to a lack of studies where NKG2D is eliminated exclusively in these cells. Here we studied the impact of NKG2D on effector CD8+ T-cell formation. NKG2D-deficiency that is restricted to murine CD8+ T cells did not impair antigen-specific T-cell expansion following mCMV and LCMV infection, but reduced their capacity to produce cytokines. Upon infection, conventional dendritic cells induce NKG2D ligands, which drive cytokine production on CD8+ T cells via the Da…

IFI16 reduced expression is correlated with unfavorable outcome in chronic lymphocytic leukemia.

2017

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Its clinical course is typically indolent; however, based on a series of pathobiological, clinical, genetic, and phenotypic parameters, patient survival varies from less than 5 to more than 20 years. In this paper, we show for the first time that the expression of the interferon-inducible DNA sensor IFI16, a member of the PYHIN protein family involved in proliferation inhibition and apoptosis regulation, is associated with the clinical outcome in CLL. We studied 99 CLLs cases by immunohistochemistry and 10 CLLs cases by gene expression profiling. We found quite variable degrees of IFI16 expression among CLLs cases. No…

2016

Interleukin-1 (IL-1) plays a crucial role in numerous inflammatory diseases via action on its only known signaling IL-1 receptor type 1 (IL-1R1). To investigate the role of IL-1 signaling in selected cell types, we generated a new mouse strain in which exon 5 of the Il1r1 gene is flanked by loxP sites. Crossing of these mice with CD4-Cre transgenic mice resulted in IL-1R1 loss of function specifically in T cells. These mice, termed IL-1R1ΔT, displayed normal development under steady state conditions. Importantly, isolated CD4 positive T cells retained their capacity to differentiate toward Th1 or Th17 cell lineages in vitro, and strongly proliferated in cultures supplemented with either ant…

TCR signalling network organization at the immunological synapses of murine regulatory T cells.

2017

Regulatory T (Treg) cells require T-cell receptor (TCR) signalling to exert their immunosuppressive activity, but the precise organization of the TCR signalling network compared to conventional T (Tconv) cells remains elusive. By using accurate mass spectrometry and multi-epitope ligand cartography (MELC) we characterized TCR signalling and recruitment of TCR signalling components to the immunological synapse (IS) in Treg cells and Tconv cells. With the exception of Themis which we detected in lower amounts in Treg cells, other major TCR signalling components were found equally abundant, however, their phosphorylation-status notably discriminates Treg cells from Tconv cells. Overall, this s…

T cells expressing a chimeric antigen receptor that binds hepatitis B virus envelope proteins control virus replication in mice.

2013

Background & Aims Antiviral agents suppress hepatitis B virus (HBV) replication but do not clear the infection. A strong effector T-cell response is required to eradicate HBV, but this does not occur in patients with chronic infection. T cells might be directed toward virus-infected cells by expressing HBV-specific receptors and thereby clear HBV and help to prevent development of liver cancer. In mice, we studied whether redirected T cells can engraft after adoptive transfer, without prior T-cell depletion, and whether the large amounts of circulating viral antigens inactivate the transferred T cells or lead to uncontrolled immune-mediated damage. Methods CD8 + T cells were isolated from m…

Analysis of chronic lymphotic leukemia transcriptomic profile: differences between molecular subgroups

2009

B cell chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder with a variable clinical course. Patients with unmutated IgV(H) gene show a shorter progression-free and overall survival than patients with immunoglobulin heavy chain variable regions (IgV(H)) gene mutated. In addition, BCL6 mutations identify a subgroup of patients with high risk of progression. Gene expression was analysed in 36 early-stage patients using high-density microarrays. Around 150 genes differentially expressed were found according to IgV(H) mutations, whereas no difference was found according to BCL6 mutations. Functional profiling methods allowed us to distinguish KEGG and gene ontology terms showing…

Study of the Expression of Angiogenic Factors and Dopaminergic Receptors: Correlation with ZAP70, CD38 and the Mutational State in Chronic Lymphocyti…

2006

Abstract The angiogenesis is a well known process implicate in the progression of CLL. In this disease has been described an increase of angiogenic and pro-angiogenic factors in serum and angiogenic receptors in B cells, mainly in advances stages. Recently had been known that the agonist of the dopaminergic receptor D2 can inhibit the tumour growth and a possible mechanism mediator is the internalization of VEGFR-2. The aim of this work had been to analyze the expression of the dopaminergic receptors (D1, D2, D3, D4 and D5), the angiogenic receptors and its correlation with the main biological factor implicated in the illness (ZAP-70, CD38 and the mutational status of IgVH/BCL-6). We had de…

Function of Dipeptidyl Peptidase IV (CD26, Tp103) in Transfected Human T Cells

1993

CD26 (Tp103) is a proteolytic enzyme (dipeptidyl peptidase IV) expressed on the T cell surface that defines an alternative activation signal for human T lymphocytes. It is absent from or present in only low amounts on resting T cells but it is expressed strongly after activation. Crosslinking of CD26/Tp103 via the monoclonal antibody CB.1 triggers functional activities in preactivated T cells. To study the molecular requirements for T cell activation via CD26 we transfected a cDNA encoding CD26 into several CD26-negative cells. In Jurkat T cell leukemia cells that normally do not express the CD26 antigen, the transfected CD26 molecule is functional because the monoclonal antibody CB.1 induc…

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…

Direct Cellular Interaction with Activated CD4+T Cells Overcomes Hyporesponsiveness of B-Cell Chronic Lymphocytic Leukemiain Vitro

1998

The proliferative response of clonal B cells from patients with chronic lymphocytic leukemia (B-CLL) is drastically reduced compared to normal B lymphocytes stimulated via the B cell antigen receptor complex or by CD40 ligation. In the present study we demonstrate that hyporesponsiveness of CLL-B cells can be overcome by stimulatory pathways mediated by activated CD4(+) T cells. In contrast to CD40 ligation, costimulation with activated T cells promotes a proliferative response in CLL-B cells identical to that in normal B cells. Furthermore, coculture with activated T cells improved survival of CLL-B cells in vitro. Differentiation of CLL-B cells into IgM producing cells was promoted, as we…