Search results for "Granzyme B"
showing 10 items of 14 documents
IL-10 signaling prevents gluten-dependent intraepithelial CD4(+) cytotoxic T lymphocyte infiltration and epithelial damage in the small intestine
2019
Breach of tolerance to gluten leads to the chronic small intestinal enteropathy celiac disease. A key event in celiac disease development is gluten-dependent infiltration of activated cytotoxic intraepithelial lymphocytes (IELs), which cytolyze epithelial cells causing crypt hyperplasia and villous atrophy. The mechanisms leading to gluten-dependent small intestinal IEL infiltration and activation remain elusive. We have demonstrated that under homeostatic conditions in mice, gluten drives the differentiation of anti-inflammatory T cells producing large amounts of the immunosuppressive cytokine interleukin-10 (IL-10). Here we addressed whether this dominant IL-10 axis prevents gluten-depend…
Study of mechanisms of action of an immunotherapy by triacyl lipid A in humans
2013
Immunotherapy acting at the primary tumor site and preventing the development of metastases is one of the strategies for treatment of patients with cancer. To improve the efficiency of the latter, it is necessary to understand how it induces tumor cell death. In the laboratory, it was observed the cure of PROb tumors in rats BDIX by the triacyl lipid A. It has been shown that this effect involved the immune system involving interactions with TLRs present in many tumor cells and innate immunity cells such as neutrophils.In this work, we investigated the possible involvement of neutrophils in the antitumor activity of triacyl lipid A in humans.In a Phase 1 study in patients with refractory so…
Characterization of the Microenvironment in Positive and Negative Sentinel Lymph Nodes from Melanoma Patients
2015
Melanomas are aggressive skin tumors characterized by high metastatic potential. Our previous results indicate that Natural Killer (NK) cells may control growth of melanoma. The main defect of blood NK cells was a decreased expression of activating NCR1/NKp46 receptor and a positive correlation of NKp46 expression with disease outcome in stage IV melanoma patients was found. In addition, in stage III melanoma patients, we identified a new subset of mature NK cells in macro-metastatic Lymph nodes (LN). In the present studies, we evaluated the numbers of NK cells infiltrating primary cutaneous melanoma and analyzed immune cell subsets in a series of sentinel lymph nodes (SLN). First, we show …
Peroxisome proliferator-activated receptor alpha deficiency impairs regulatory T cell functions: Possible application in the inhibition of melanoma t…
2016
International audience; Regulatory T (Treg) cells are important to induce and maintain immunological self-tolerance. Although the progress accomplished in understanding the functional mechanism of Treg cells, intracellular molecules that control the mechanisms of their suppressive capacity are still on investigation. The present study showed that peroxisome proliferator-activated receptor-alpha deficiency impaired the suppressive activity of Treg cells on CD4(+)CD25(-) and CD8(+) T cell proliferation. In Treg cells, PPARα gene deletion also induced a decrease of migratory abilities, and downregulated the expression of chemokine receptors (CCR-4, CCR-8 and CXCR-4) and p27(KIP1) mRNA. Treg ce…
Etude des mécanismes d'action d'une immunothérapie par un lipide A, seul ou associé à l'oxaliplatine, dans des modèles de cancers coliques
2013
Colorectal cancer is a major public health concern in France. Resistance to standard chemotherapy requires development of novel therapeutic approaches. In the past decades, our team showed the immunotherapeutic properties of lipid A in a model of colon cancer in rats. 95% of rats bearing small carcinomas were cured following treatment by lipid A. The study of mechanisms underlying this immunotherapy allowed us to show that the antitumor effect of lipid A was dependent on cytotoxicity induced by granzyme B produced by intratumoral neutrophils. Indeed, we have shown that, in the tumor microenvironment, neutrophils produced granzyme B and had a pro-tumorigenic N2 phenotype. When rats were trea…
Invariant natural killer T cells act as an extravascular cytotoxic barrier for joint-invading Lyme Borrelia
2014
CXCR6-GFP(+) cells, which encompass 70% invariant natural killer T cells (iNKT cells), have been found primarily patrolling inside blood vessels in the liver. Although the iNKT cells fail to interact with live pathogens, they do respond to bacterial glycolipids presented by CD1d on liver macrophage that have caught the microbe. In contrast, in this study using dual laser multichannel spinning-disk intravital microscopy of joints, the CXCR6-GFP, which also made up 60-70% iNKT cells, were not found in the vasculature but rather closely apposed to and surrounding the outside of blood vessels, and to a lesser extent throughout the extravascular space. These iNKT cells also differed in behavior,…
Neuroinflammation by cytotoxic T-lymphocytes impairs retrograde axonal transport in an oligodendrocyte mutant mouse.
2012
Mice overexpressing proteolipid protein (PLP) develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonal transport. PLP overexpression in the absence of T-lymphocytes rescued retrograde axonal transport defects and abolished axonal swellings. Bone marrow tr…
B CELL CHANGES IN AGING
2014
The aging of the immune system is a gradual and dynamic process that modifies some immunological functions. These changes are known as “immunosenescence” that have a great impact on immune performance in late life, contributing to the decreased ability of the elderly people to respond to emerging pathogens and to the decreased responsiveness to vaccinations. It is known that the adaptive immune functions are affected in the aged. In particular, with aging, the acquired compartment of the immune system shows significant modifications in both T and B cell branches. Thus, the adaptive immune response of elderly people is qualitatively and quantitatively reduced when compared to that observed i…
Serological identification of HSP105 as a novel non-Hodgkin lymphoma therapeutic target.
2011
Abstract We reported that the clinical efficacy of dendritic cell–based vaccination is strongly associated with immunologic responses in relapsed B-cell non-Hodgkin lymphoma (B-NHL) patients. We have now investigated whether postvaccination antibodies from responders recognize novel shared NHL-restricted antigens. Immunohistochemistry and flow cytometry showed that they cross-react with allogeneic B-NHLs at significantly higher levels than their matched prevaccination samples or nonresponders' antibodies. Western blot analysis of DOHH-2 lymphoma proteome revealed a sharp band migrating at approximately 100 to 110 kDa only with postvaccine repertoires from responders. Mass spectrometry ident…
Differentiation, phenotype, and function of interleukin-17-producing human Vγ9Vδ2 T cells.
2011
Abstract In healthy adults, the major peripheral blood γδ T-cell subset expresses the Vγ9Vδ2 TCR and displays pleiotropic features. Here we report that coculture of naive Vγ9Vδ2 T cells with phosphoantigens and a cocktail of cytokines (IL-1-β, TGF-β, IL-6, and IL-23), leads to selective expression of the transcription factor RORγt and polarization toward IL-17 production. IL-17+ Vγ9Vδ2 T cells express the chemokine receptor CCR6 and produce IL-17 but neither IL-22 nor IFN-γ; they have a predominant terminally differentiated (CD27−CD45RA+) phenotype and express granzyme B, TRAIL, FasL, and CD161. On antigen activation, IL-17+ Vγ9Vδ2 T cells rapidly induce CXCL8-mediated migration and phagocy…