Opioid receptor blockade increases the number of lymphocytes without altering T cell response in draining lymph nodes in vivo

2007 ◽  
Vol 188 (1-2) ◽  
pp. 95-102 ◽  
Author(s):  
Martial Jaume ◽  
Sophie Laffont ◽  
Emmanuelle Chapey ◽  
Catherine Blanpied ◽  
Gilles Dietrich
Blood ◽  
2005 ◽  
Vol 105 (11) ◽  
pp. 4226-4234 ◽  
Author(s):  
Lixin Wang ◽  
Eric Dobrzynski ◽  
Alexander Schlachterman ◽  
Ou Cao ◽  
Roland W. Herzog

Abstract Adeno-associated viral (AAV) vectors have been successfully used for therapeutic expression of systemic transgene products (such as factor IX or erythropoietin) following in vivo administration to skeletal muscle of animal models of inherited hematologic disorders. However, an immune response may be initiated if the transgene product represents a neoantigen. Here, we use ovalbumin (OVA) as a model antigen and demonstrate immune-mediated elimination of expression on muscle-directed AAV-2 gene transfer. Administration to immune competent mice resulted in transient systemic OVA expression. Within 10 days, OVA-specific T-helper cells had been activated in draining lymph nodes, an inflammatory immune response ensued, and OVA-expressing muscle fibers were destroyed by a cytotoxic CD8+ T-cell response. Use of a muscle-specific promoter did not prevent this immune response. Adoptively transferred CD4+ cells transgenic for a T-cell receptor specific to OVA peptide-major histocompatibility complex class II showed antigen-specific, vector dose-dependent proliferation confined to the draining lymph nodes of AAV-OVA–transduced muscle within 5 days after gene transfer and subsequently participated in lymphocytic infiltration of transduced muscle. This study documents that a local immune response limits sustained expression of a secreted protein in muscle gene transfer, a finding that may have consequences for design of clinical protocols.


2012 ◽  
Vol 278 (1-2) ◽  
pp. 158-165 ◽  
Author(s):  
Tamás Kobezda ◽  
Sheida Ghassemi-Nejad ◽  
Tibor T. Glant ◽  
Katalin Mikecz

2004 ◽  
Vol 172 (2) ◽  
pp. 981-988 ◽  
Author(s):  
Edward M. Bertram ◽  
Wojciech Dawicki ◽  
Bradley Sedgmen ◽  
Jonathan L. Bramson ◽  
David H. Lynch ◽  
...  

2020 ◽  
Author(s):  
Melisa Gorosito Serrán ◽  
Facundo Fiocca Vernengo ◽  
Laura Almada ◽  
Cristian G Beccaria ◽  
Pablo F Canete ◽  
...  

ABSTRACTDuring infections with protozoan parasites or virus, T cell immunosuppression is generated simultaneously with a high B cell activation. Here, we show that in T. cruzi infection, all plasmablasts detected had higher surface expression of PD-L1, than other mononuclear cells. PD-L1hi plasmablasts were induced in vivo in an antigen-specific manner and required help from Bcl-6+CD4+T cells. PD-L1hi expression was not a characteristic of all antibody-secreting cells since plasma cells found during the chronic phase of infection express PD-L1 but at lower levels. PD-L1hi plasmablasts were also present in mice infected with Plasmodium or with lymphocytic choriomeningitis virus, but not in mice with autoimmune disorders or immunized with T cell-dependent antigens. PD-L1hi plasmablasts suppressed T cell response, via PD-L1, in vitro and in vivo. Thus, this study reveals that extrafollicular PD-L1hi plasmablasts, which precede the germinal center (CG) response, are a suppressive population in infections that may influence T cell response.Brief summaryPathogens develop different strategies to settle in the host. We identified a plasmablats population induced by pathogens in acute infections which suppress T cell response.


Gene Therapy ◽  
2007 ◽  
Vol 14 (20) ◽  
pp. 1481-1491
Author(s):  
S Cayeux ◽  
B Bukarica ◽  
C Buschow ◽  
J Charo ◽  
M Bunse ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1284
Author(s):  
Natalia Trempolec ◽  
Charline Degavre ◽  
Bastien Doix ◽  
Davide Brusa ◽  
Cyril Corbet ◽  
...  

For poorly immunogenic tumors such as mesothelioma there is an imperious need to understand why antigen-presenting cells such as dendritic cells (DCs) are not prone to supporting the anticancer T cell response. The tumor microenvironment (TME) is thought to be a major contributor to this DC dysfunction. We have reported that the acidic TME component promotes lipid droplet (LD) formation together with epithelial-to-mesenchymal transition in cancer cells through autocrine transforming growth factor-β2 (TGF-β2) signaling. Since TGF-β is also a master regulator of immune tolerance, we have here examined whether acidosis can impede immunostimulatory DC activity. We have found that exposure of mesothelioma cells to acidosis promotes TGF-β2 secretion, which in turn leads to LD accumulation and profound metabolic rewiring in DCs. We have further documented how DCs exposed to the mesothelioma acidic milieu make the anticancer vaccine less efficient in vivo, with a reduced extent of both DC migratory potential and T cell activation. Interestingly, inhibition of TGF-β2 signaling and diacylglycerol O-acyltransferase (DGAT), the last enzyme involved in triglyceride synthesis, led to a significant restoration of DC activity and anticancer immune response. In conclusion, our study has identified that acidic mesothelioma milieu drives DC dysfunction and altered T cell response through pharmacologically reversible TGF-β2-dependent mechanisms.


1987 ◽  
Vol 68 (7) ◽  
pp. 2001-2006 ◽  
Author(s):  
A. M. Kesson ◽  
R. V. Blanden ◽  
A. Mullbacher

PLoS ONE ◽  
2009 ◽  
Vol 4 (4) ◽  
pp. e5187 ◽  
Author(s):  
Ilaria Sauzullo ◽  
Fabio Mengoni ◽  
Miriam Lichtner ◽  
Anna Paola Massetti ◽  
Raffaella Rossi ◽  
...  

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