223 research outputs found
Erbb2 DNA vaccine combined with Treg cell deletion enhances antibody response and reveals latent low-avidity T cells. Potential and limits of its therapeutic efficacy
No full textestroy after use. Rat (r) Erbb2 transgenic BALB-neuT mice genetically predestined to develop multiple invasive carcinomas allow an assessment of the potential of a vaccine against the stages of cancer progression. Due to Erbb2 expression in the thymus and its over-expression in the mammary gland, CD8 + T cell clones reacting at high avidity with dominant Erbb2 epitopes are deleted in these mice. In BALB-neuT mice with diffuse and invasive in situ lesions and almost palpable carcinomas, a temporary Treg cells depletion combined with anti-rErbb2 vaccine markedly enhanced the antirErbb2 antibody response and allowed the expansion of latent pools of low-avidity CD8 + T cells bearing T cell receptors repertoire reacting with the rErbb2 dominant peptide. This combination of a higher antibody response and activation of a low-avidity cytotoxic response persistently blocked tumor progression at stages in which the vaccine alone was ineffective. However, when diffuse and invasive microscopic cancers become almost palpable this combination was no longer able to secure a significant extension of mice survival
Distinct and Non-Overlapping T Cell Receptor Repertoires Expanded by DNA Vaccination in Wild-Type and HER-2 Transgenic BALB/c Mice.
No full textCentral tolerance to tumor-associated Ags is an immune-escape mechanism that significantly limits the TCR repertoires available for tumor eradication. The repertoires expanded in wild-type BALB/c and rat-HER-2/neu (rHER-2) transgenic BALB-neuT mice following DNA immunization against rHER-2 were compared by spectratyping the variable (V)beta and the joining (J)beta CDR 3. Following immunization, BALB/c mice raised a strong response. Every mouse used one or more CD8(+) T cell rearrangements of the Vbeta9-Jbeta1.2 segments characterized by distinct length of the CDR3 and specific for 63-71 or 1206-1214 rHER-2 peptides. In addition, two CD4(+) T cell rearrangements recurred in >50% of mice. Instead, BALB-neuT mice displayed a limited response to rHER-2. Their repertoire is smaller and uses different rearrangements confined to CD4(+) T cells. Thus, central tolerance in BALB-neuT mice acts by silencing the BALB/c mice self-reactive repertoire and reducing the size of the CD8(+) T cell component. CD8(+) and CD4(+) T cells from both wild-type and transgenic mice home to tumors. This definition of the T cell repertoires available is critical to the designing of immunological maneuvers able to elicit an effective immune reaction against HER-2-driven carcinogenesis
L’equo processo tra Corte europea e Corte costituzionale italiana. Il caso delle immunità parlamentari
No full textLa Corte Suprema del Canada e l’art. 1 della Carta dei diritti. Una “free and democratic society” in continua evoluzione
No full textAdenosine A2a receptor stimulation blocks development of nonalcoholic steatohepatitis in mice by multilevel inhibition of signals that cause immunolipotoxicity
No full textLipotoxicity and immunoinflammation are associated with the evolution of steatosis toward nonalcoholic steatohepatitis (NASH). This study reports the ability of adenosine A2a receptor (A2aR) activation to inhibit NASH development by modulating the responses of CD4(+) T-helper (Th) cells to avoid an immuno-mediated potentiation of lipotoxicity. The effect of the A2aR agonist CGS21680 on immunoinflammatory signals, CD4(+)Th cell infiltration and immunolipotoxicity was analyzed in steatotic C57BL/6 mice fed with a methionine-choline-deficient (MCD) diet and in mouse hepatocytes exposed to palmitic acid (PA). CGS21680 inhibited NASH development in steatotic mice and decreased cytokines and chemokines involved in Th cell recruitment or polarization (namely CXCL10, CCL2, tumor necrosis factor alfa [TNFα], tumor growth factor [TGFβ], and IL-12). CGS21680 also reduced the expansion of Th17, Th22, and Th1 cells and increased the immunosuppressive activity of T regulatory cells. In PA-treated mice hepatocytes, CGS21680 inhibited the production of CXCL10, TNFα, TGFβ, IL-12, and CCL2; CGS21680 also prevented JNK-dependent lipotoxicity and its intensification by IL-17 or IL-17 plus IL-22 through Akt/PI3-kinase stimulation and inhibition of the negative regulator of PI3-kinase, (phosphatase and tensin homologue deleted from chromosome 10 (PTEN), which is upregulated by IL-17. In MCD livers, CGS21680 reduced JNK activation and PTEN expression and increased Akt phosphorylation. In conclusion, A2aR stimulation inhibited NASH development by reducing Th17 cell expansion and inhibiting the exacerbation of the IL-17-induced JNK-dependent lipotoxicity. These data promote the implementation of further studies to evaluate the potential clinical application of A2aR agonists that, by being able to function as both cytoprotective and immunomodulatory agents, could efficiently antagonize the multi-faced pathogenesis of NASH
Il principio democratico tra crisi, ideali ed effettive realizzazioni. Una riflessione comparata
No full textSupplemental Material - Endovascular treatment of patients with acute ischemic stroke and tandem occlusion due to internal carotid artery dissection: A multicenter experience
No full textSupplemental Material for Endovascular treatment of patients with acute ischemic stroke and tandem occlusion due to internal carotid artery dissection: A multicenter experience by Valerio Da Ros, Federica Pusceddu, Simona Lattanzi, Jacopo Scaggiante, Fabrizio Sallustio, Federico Marrama, Monica Bandettini di Poggio, Gianpaolo Toscano, Francesca Di Giuliano, Claudia Rolla-Bigliani, Maria Ruggiero, Niccolo Haznedari, Alessandro Sgreccia, Giuseppina Sanfilippo, Cinzia Finocchi, Marina Diomedi, Santino O Tomasi, Paolo Palmisciano, Giuseppe E Umana, Lidia Strigari, Christoph J Griessenauer, Francesca Pitocchi, Francesco Garaci, Roberto Floris in The Neuroradiology Journal</p
Title: Acute respiratory distress in a neutropenic febrile patient after Hematopoietic Cell Transplantation
No full textAcute respiratory distress in a neutropenic febrile patient after hematopoietic cell transplantation
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