scholarly journals Induction of Immune Tolerance in Asthmatic Mice by Vaccination with DNA Encoding an Allergen–Cytotoxic T Lymphocyte-Associated Antigen 4 Combination

2011 ◽  
Vol 18 (5) ◽  
pp. 807-814 ◽  
Author(s):  
Fang Zhang ◽  
Gang Huang ◽  
Bo Hu ◽  
Yong Song ◽  
Yi Shi
Keyword(s):  
Airway Inflammation ◽  
Dna Vaccine ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Treg Cells ◽  
Airway Hyperreactivity ◽  
Interleukin 4 ◽  
High Dose ◽  
Dna Encoding ◽  
Allergen Specific Immunotherapy

ABSTRACTAllergen-specific immunotherapy is a potential treatment for allergic diseases. We constructed an allergen–cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-encoding DNA vaccine, administered it directly to antigen-presenting cells (APCs), and investigated its ability and mechanisms to ameliorate allergic airway inflammation in an asthmatic mouse model. An allergen-CTLA-4 DNA plasmid (OVA-CTLA-4-pcDNA3.1) encoding an ovalbumin (OVA) and the mouse CTLA-4 extracellular domain was constructed and transfected into COS-7 cells to obtain the fusion protein OVA-CTLA-4, which was able to bind the B7 ligand on dendritic cells (DCs), and induced CD25+Foxp3+regulatory T (Treg) cells by the coculture of naive CD4+T cells with DCsin vitro. In an animal study, BALB/c mice were sensitized and challenged with OVA to establish the asthmatic model. Vaccination with a high dose of OVA-CTLA-4-pcDNA3.1significantly decreased interleukin-4 (IL-4) and IL-5 levels and eosinophil counts and prevented OVA-induced reduction of the gamma interferon level in the bronchoalveolar lavage fluid. In addition, these mice suffered less severe airway inflammation and had lower levels of OVA-specific IgE and IgG1 titers in serum. Also, high-dose OVA-CTLA-4-pcDNA3.1vaccination inhibited the development of airway hyperreactivity and prevented OVA-induced reduction of the percentages of Foxp3+Treg cells in the spleen. Our results indicate that a high dose of allergen-CTLA-4-encoding DNA vaccine was more effective in preventing an allergen-induced Th2-skewed immune response through the induction of Treg cells and may be a new alternative therapy for asthma.

scholarly journals TGF-β1 drives Th9 but not Treg cells upon allergen exposure

2021 ◽  
Author(s):  
Stephanie Musiol ◽  
Francesca Alessandrini ◽  
Constanze A. Jakwerth ◽  
Adam M. Chaker ◽  
Evelyn Schneider ◽  
...  
Keyword(s):  
T Cells ◽  
Therapeutic Option ◽  
Treg Cells ◽  
Allergen Exposure ◽  
Airway Hyperreactivity ◽  
Allergen Specific Immunotherapy ◽  
Genetic Ablation ◽  
Th9 Cells ◽  
Tgf Β1 ◽  
Th9 Cell

TGF-β1 is known to have a pro-inflammatory impact by inducing Th9 cells, while it also induces anti-inflammatory Treg cells (Tregs). In the context of allergic airway inflammation (AAI) its dual role can be of critical importance in influencing the outcome of the disease. Here we demonstrate that TGF-β acts in AAI by driving effector T cells into Th9 cells, while Tregs differentiate independently. Induction of experimental AAI and airway hyperreactivity in a mouse model with inducible genetic ablation of the TGFβ-receptor 2 (TGFBR2) on CD4+T cells significantly reduced the disease phenotype. Further, it blocked the induction of Th9 cell frequencies, but increased Treg cells. To translate these findings into a human clinically relevant context, Th9 and Treg cells were quantified both locally in induced sputum and systemically in blood of allergic rhinitis and asthma patients with or without allergen-specific immunotherapy (AIT). Natural allergen exposure induced local and systemic Th2, Th9 cell and reduced Tregs, while therapeutic allergen exposure by AIT suppressed Th2 and Th9 cell frequencies along with TGF-β and IL-9 secretion. Altogether, these findings support that neutralization of TGF-β represents a viable therapeutic option in allergy and asthma, not posing the risk of immune dysregulation by impacting Tregs.

Estimation of associations between 10 common gene polymorphisms and gastric cancer: evidence from a meta-analysis

2019 ◽  
Vol 73 (6) ◽  
pp. 318-321
Author(s):  
Zongjing Xie ◽  
Bingmei Wang ◽  
Yongjie Chai ◽  
Junyin Chen
Keyword(s):  
Gastric Cancer ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Meta Analysis ◽  
Interleukin 4 ◽  
East Asians ◽  
Mannose Binding ◽  
Binding Lectin ◽  
Positive Results ◽  
Review Manager

AimsAssociations between polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)/mannose-binding lectin (MBL)/interleukin-4 (IL-4)/interleukin-6 (IL-6)/phospholipase C ε−1 (PLCE1) and gastric cancer (GC) were already reported by many studies, yet the conclusions of these studies were somehow controversial. The aim of this meta-analysis was to better clarify associations between polymorphisms in CTLA-4/MBL/IL-4/IL-6/PLCE1 and GC by combing the results of all relevant studies.MethodsEligible studies were searched from PubMed, Embase, WOS and CNKI. We used Review Manager to combine the results of individual studies.ResultsForty-three studies were included in this meta-analysis. Combined results revealed that CTLA-4 rs5742909 (dominant comparison: OR: 1.58, 95 % CI: 1.01 to 2.48; allele comparison: OR: 1.69, 95 % CI: 1.12 to 2.56) and PLCE1 rs2274223 (dominant comparison: OR: 0.84, 95 % CI: 0.72 to 0.98; recessive comparison: OR: 1.23, 95 % CI: 1.08 to 1.40; over-dominant comparison: OR: 1.16, 95 % CI: 1.00 to 1.34; allele comparison: OR 0.88, 95 % CI 0.78 to 0.99) polymorphisms were significantly associated with GC in the general population. We also obtained similar significant associations with GC for rs5742909 and rs2274223 polymorphisms in East Asians. Nevertheless, no positive results were observed for the other eight investigated polymorphisms.ConclusionCollectively, this meta-analysis demonstrated that CTLA-4 rs5742909 and PLCE1 rs2274223 polymorphisms may confer susceptibility to GC, especially for East Asians.

Induction of multiple cytotoxic T lymphocyte responses in mice by a multiepitope DNA vaccine against dengue virus serotype 1

2016 ◽  
Vol 60 (12) ◽  
pp. 835-845 ◽  
Author(s):  
Xin Yu Chen ◽  
De Zhou Li ◽  
Xiao Zhi Zhong ◽  
Bokun Chen ◽  
Zhi Liang Duan ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dna Vaccine ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Virus Serotype ◽  
Serotype 1 ◽  
Lymphocyte Responses ◽  
Dengue Virus Serotype 1

scholarly journals Magnitude and Diversity of Cytotoxic-T-Lymphocyte Responses Elicited by Multiepitope DNA Vaccination in Rhesus Monkeys

2003 ◽  
Vol 77 (18) ◽  
pp. 10113-10118 ◽  
Author(s):  
Ramu A. Subbramanian ◽  
Marcelo J. Kuroda ◽  
William A. Charini ◽  
Dan H. Barouch ◽  
Cristina Costantino ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
T Lymphocyte ◽  
Plasmid Dna ◽  
High Frequency ◽  
Cytotoxic T Lymphocyte ◽  
Monkey Model ◽  
Modified Vaccinia Virus Ankara ◽  
Immunodeficiency Virus ◽  
Plasmid Dna Vaccine ◽  
Ctl Responses

ABSTRACT In an effort to develop an AIDS vaccine that elicits high-frequency cytotoxic-T-lymphocyte (CTL) responses with specificity for a diversity of viral epitopes, we explored two prototype multiepitope plasmid DNA vaccines in the simian-human immunodeficiency virus/rhesus monkey model to determine their efficiency in priming for such immune responses. While a simple multiepitope vaccine construct demonstrated limited immunogenicity in monkeys, this same multiepitope genetic sequence inserted into an immunogenic simian immunodeficiency virus gag DNA vaccine elicited high-frequency CTL responses specific for all of the epitopes included in the vaccine. Both multiepitope vaccine prototypes primed for robust epitope-specific CTL responses that developed following boosting with recombinant modified vaccinia virus Ankara vaccines expressing complete viral proteins. The natural hierarchy of immunodominance for these epitopes was clearly evident in the boosted monkeys. These studies suggest that multiepitope plasmid DNA vaccine-based prime-boost regimens can efficiently prime for CTL responses of increased breadth and magnitude, although they do not overcome predicted hierarchies of immunodominance.

scholarly journals Early Interleukin 4–Dependent Response Can Induce Airway Hyperreactivity before Development of Airway Inflammation in a Mouse Model of Asthma

2001 ◽  
Vol 81 (10) ◽  
pp. 1385-1396 ◽  
Author(s):  
Yasuo To ◽  
Makoto Dohi ◽  
Ryoichi Tanaka ◽  
Atsushi Sato ◽  
Kazuyuki Nakagome ◽  
...  
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Airway Hyperreactivity ◽  
Interleukin 4

scholarly journals Papillomavirus Pseudovirus: a Novel Vaccine To Induce Mucosal and Systemic Cytotoxic T-Lymphocyte Responses

2001 ◽  
Vol 75 (21) ◽  
pp. 10139-10148 ◽  
Author(s):  
Wei Shi ◽  
Jianzhong Liu ◽  
Yujun Huang ◽  
Liang Qiao
Keyword(s):  
Dna Vaccine ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Oral Immunization ◽  
Lymphocytic Choriomeningitis ◽  
Lymphoid Tissues ◽  
Adjuvant Effect ◽  
Ctl Response ◽  
Lymphocyte Responses ◽  
Ctl Responses

ABSTRACT Intestinal mucosa is a portal for many infectious pathogens. Systemic immunization, in general, does not induce a cytotoxic T-lymphocyte (CTL) response at the mucosal surface. Because papillomavirus (PV) naturally infects mucosa and skin, we determined whether PV pseudovirus, i.e., PV-like particles in which unrelated DNA plasmids are packaged, could generate specific mucosal immunity. We found that the pseudovirus that encoded the lymphocytic choriomeningitis virus gp33 epitope induced a stronger CTL response than a DNA vaccine (plasmid) encoding the same epitope given systemically. The virus-like particles that were used to make the pseudoviruses provided an adjuvant effect for induction of CTLs by the DNA vaccine. The PV pseudovirus pseudoinfected mucosal and systemic lymphoid tissues when administered orally. Oral immunization with the pseudovirus encoding human PV type 16 mutant E7 induced mucosal and systemic CTL responses. In comparison, a DNA vaccine encoding E7, when given orally, did not induce a CTL response in intestinal mucosal lymphoid tissue. Further, oral immunization with the human PV pseudovirus encoding E7 protected mice against mucosal challenge with an E7-expressing bovine PV pseudovirus. Thus, PV pseudovirus can be used as a novel vaccine to induce mucosal and systemic CTL responses.

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