ArticleInfection and immunity2009
Perforin and gamma interferon expression are required for CD4+ and CD8+ T-cell-dependent protective immunity against a human parasite, Trypanosoma cruzi, elicited by heterologous plasmid DNA prime-recombinant adenovirus 5 boost vaccination.
Article in Infection and immunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 99 citations in OpenAlex.
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- Immunomodulatory activity of Trypanosoma cruzi recombinant antigen combination TSA-1-C4 and Tc24-C4 induce activation of macrophages and CD8Parasitology research · 2025Article
- Trypanosoma cruzi Tc24 Antigen Expressed and Orally Delivered by Schizochytrium sp. Microalga is Immunogenic in Mice.Molecular biotechnology · 2024Article
- ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas' disease.NPJ vaccines · 2023Article
- Recent Advances in the Development of Adenovirus-Vectored Vaccines for Parasitic Infections.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Vaccine-linked chemotherapy with a low dose of benznidazole plus a bivalent recombinant protein vaccine prevents the development of cardiac fibrosis caused by Trypanosoma cruzi in chronically-infected BALB/c mice.PLoS neglected tropical diseases · 2022Article
- Cellular Stress and Senescence Induction duringTropical medicine and infectious disease · 2022Review
- T-Cell Subpopulations Exhibit Distinct Recruitment Potential, Immunoregulatory Profile and Functional Characteristics in Chagas versus Idiopathic Dilated Cardiomyopathies.Frontiers in cardiovascular medicine · 2022Article
- Host-parasite dynamics in Chagas disease from systemic to hyper-local scales.Parasite immunology · 2021Review
- Rapamycin Improves the Response of Effector and Memory CD8Frontiers in cellular and infection microbiology · 2021Article
- CD8Frontiers in cellular and infection microbiology · 2021Article
- CD8low T cells expanded following acute Trypanosoma cruzi infection and benznidazole treatment are a relevant subset of IFN-γ producers.PLoS neglected tropical diseases · 2020Article
- CXCR3 chemokine receptor contributes to specific CD8+ T cell activation by pDC during infection with intracellular pathogens.PLoS neglected tropical diseases · 2020Article
- São Paulo School of Advanced Sciences on Vaccines: an overview.The journal of venomous animals and toxins including tropical diseases · 2020Review
- Understanding CD8Trends in parasitology · 2019Review
- CXCR3 chemokine receptor guides Trypanosoma cruzi-specific T-cells triggered by DNA/adenovirus ASP2 vaccine to heart tissue after challenge.PLoS neglected tropical diseases · 2019Article
- Intracellular Pathogens: Host Immunity and Microbial Persistence Strategies.Journal of immunology research · 2019Review
- Thymic expression of IL-4 and IL-15 after systemic inflammatory or infectious Th1 disease processes induce the acquisition of "innate" characteristics during CD8+ T cell development.PLoS pathogens · 2019Article
- NLRP3 Inflammasome and Caspase-1/11 Pathway Orchestrate Different Outcomes in the Host Protection AgainstFrontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A heterologous prime-boost strategy using plasmid DNA, followed by replication-defective recombinant adenovirus 5, is being proposed as a powerful way to elicit CD4(+) and CD8(+) T-cell-mediated protective immunity against intracellular pathogens. We confirmed this concept and furthered existing research by providing evidence that the heterologous prime-boost regimen using the gene encoding amastigote surface protein 2 elicited CD4(+) and CD8(+) T-cell-mediated protective immunity (reduction of acute parasitemia and prolonged survival) against experimental infection with Trypanosoma cruzi. Protective immunity correlated with the presence of in vivo antigen-specific cytotoxic activity prior to challenge. Based on this, our second goal was to determine the outcome of infection after heterologous prime-boost immunization of perforin-deficient mice. These mice were highly susceptible to infection. A detailed analysis of the cell-mediated immune responses in immunized perforin-deficient mice showed an impaired gamma interferon (IFN-gamma) secretion by immune spleen cells upon restimulation in vitro with soluble recombinant antigen. In spite of a normal numeric expansion, specific CD8(+) T cells presented several functional defects detected in vivo (cytotoxicity) and in vitro (simultaneous expression of CD107a/IFN-gamma or IFN-gamma/tumor necrosis factor alpha) paralleled by a decreased expression of CD44 and KLRG-1. Our final goal was to determine the importance of IFN-gamma in the presence of highly cytotoxic T cells. Vaccinated IFN-gamma-deficient mice developed highly cytotoxic cells but failed to develop any protective immunity. Our study thus demonstrated a role for perforin and IFN-gamma in a number of T-cell-mediated effector functions and in the antiparasitic immunity generated by a heterologous plasmid DNA prime-adenovirus boost vaccination strategy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.