Search results for "Lymphocyte"

Inferring slowly-changing dynamic gene-regulatory networks

2015

Dynamic gene-regulatory networks are complex since the interaction patterns between their components mean that it is impossible to study parts of the network in separation. This holistic character of gene-regulatory networks poses a real challenge to any type of modelling. Graphical models are a class of models that connect the network with a conditional independence relationships between random variables. By interpreting these random variables as gene activities and the conditional independence relationships as functional non-relatedness, graphical models have been used to describe gene-regulatory networks. Whereas the literature has been focused on static networks, most time-course experi…

PD‐1‐induced T cell exhaustion is controlled by a Drp1‐dependent mechanism

2022

Programmed cell death‐1 (PD‐1) signaling downregulates the T‐cell response, promoting an exhausted state in tumor‐infiltrating T cells, through mostly unveiled molecular mechanisms. Dynamin‐related protein‐1 (Drp1)‐dependent mitochondrial fission plays a crucial role in sustaining T‐cell motility, proliferation, survival, and glycolytic engagement. Interestingly, such processes are exactly those inhibited by PD‐1 in tumor‐infiltrating T cells. Here, we show that PD‐1pos CD8+ T cells infiltrating an MC38 (murine adenocarcinoma)‐derived murine tumor mass have a downregulated Drp1 activity and more elongated mitochondria compared with PD‐1neg counterparts. Also, PD‐1pos lymphocytic elements in…

The non-neuronal cholinergic system

2012

Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis

2006

Familial haemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous disorder characterised by constitutive defects in cellular cytotoxicity resulting in fever, hepatosplenomegaly and cytopenia, and the outcome is fatal unless treated by chemoimmunotherapy followed by haematopoietic stem‐cell transplantation. Since 1999, mutations in the perforin gene giving rise to this disease have been identified; however, these account only for 40% of cases. Lack of a genetic marker hampers the diagnosis, suitability for transplantation, selection of familial donors, identification of carriers, genetic counselling and prenatal diagnosis. Mutations in the Munc13–4 gene have recently been des…

Pronostic role of CD4 T lymphocyte infiltrates in breast cancers

2017

Tumor escape to immune system surveillance is one of the reasons why human cancer achieves to grow. In my research team, we aim to study CD4 T cell populations and their functions in the context of cancer. My work was precisely to determine if the results obtained in mice could be transposable in humans, in the context of breast cancer. . We first unraveled that tumor infiltrating Th17 cells could inhibit effector and cytotoxic functions of Th1 and CD8 T cells in an ectonucleotidase-dependent manner. Finally, we showed that high tumor infiltration in IL-17+ cells were significantly associated with a worse clinical prognosis for breast cancer patients. Then, we aim to prevent Th17 cell diffe…

Homing and memory patterns of human gammadelta T cells in physiopathological situations.

2004

Vgamma9Vdelta2 are a heterogeneous population of T cells and comprise distinct naive, memory and effector populations that can be distinguished on the basis of surface marker expression and effector functions. We review here these recently studied features of Vgamma9Vdelta2 T lymphocyte biology and the roles they play in infectious and autoimmune diseases.

Differential activation of human γ δ cells by nonpeptide phosphoantigens

2001

Human T cells expressing Vγ9/Vδ2-encoded TCR recognize several nonpeptide phosphoantigens in the absence of major histocompatibility complex restriction. As these cells respond differentially to increasing concentrations of structurally related phosphoantigens, such ligands constitute agonists of different strengths. By analyzing early cellular events and late effector responses of γ δ T cells, we compared their patterns of stimulation by weak, medium and strong phosphoantigen agonists. We found that, although the early metabolic activation as assessed by cytosensormicrophysiometry directly reflects the intensity of subsequent effector response by γ δ cells, TCR down-modulation is dissociat…

New therapeutic strategies for treatment of inflammatory bowel disease

2008

Although the precise etiology of inflammatory bowel disease (IBD) still remains unclear, considerable progress has been made in the identification of cytokine-mediated signaling pathways involved in the inflammatory process. Recent data have clearly shown that these pathways induce augmented intestinal T-cell activation and thus resistance to apoptosis, which is a central process in disease pathogenesis, as it impairs mucosal homeostasis. Therefore, novel therapeutic strategies aim at restoring activated effector T-cell susceptibility to apoptosis in the gut, based on a pathophysiological rationale. This development is best exemplified by the emergence of agents that target the TNF pathway,…

IL-12 family members in experimental colitis

2008

Interleukin (IL)-12 p35/p40 is a heterodimeric cytokine that plays an important role in T helper (Th) cell polarization and Th1 T-cell differentiation. Recent findings have shown that both p35 and p40 can form other cytokines with different proteins (IL-23: p19/p40; IL-35: p35/EBI3). Furthermore, the cytokine IL-27 (EBI3/p28) has been identified as a member of the IL-12 family. Here, we discuss the recent findings on the role of IL-12 family members in experimental colitis. In particular, the role of IL-23 as a master regulator of effector T-cell activation is highlighted. These findings have important implications for the design of new therapeutic approaches in chronic intestinal inflammat…

A D-mannose-specific lectin from Gerardia savaglia that inhibits nucleocytoplasmic transport of mRNA.

1987

A new lectin has been isolated from the coral Gerardia savaglia by affinity chromatography, using locust gum as an absorbent, and D-mannose as eluant. Final purification was achieved by Bio-Gel P300 gel filtration. The agglutinin is a protein composed of two polypeptide chains with a Mr of 14800; the two subunits are not linked by disulfide bond(s). The isoelectric point is 4.8, the amino acid composition is rich in the acidic amino acids aspartic acid and glutamic acid. The absorption maximum for the protein was at 276 nm; with a molar absorption coefficient of 1.27 X 10(5) M-1 cm-1. The lectin precipitated erythrocytes from humans (A, B and O), sheep, rabbit and carp with a titer between …