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Critical contribution of immunoproteasomes in the induction of protective immunity against Trypanosoma cruzi in mice vaccinated with a plasmid encoding a CTL epitope fused to green fluorescence protein
- Source :
- Microbes and Infection. 10:241-250
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- Acquired immunity against infection with Trypanosoma cruzi is dependent on CD8 + T cells. Here, to develop a vaccine strategy taking advantage of activated CD8 + T cells, we constructed a DNA vaccine, designated pGFP-TSA1, encoding a fusion protein linking GFP to a single CTL epitope of TSA1, a leading candidate for vaccine against T. cruzi . C57BL/6 mice vaccinated with this plasmid showed suppressed parasitemia and prolonged survival. Vaccination with pGFP-TSA1 enhanced epitope-specific cytotoxicity and IFN-γ secretion by CD8 + T cells. Furthermore, the depletion of CD8 + T cells prior to challenge infection with T. cruzi completely abolished this protection, indicating that CD8 + T cells are the principal effector T cells involved. When mice deficient in the proteasome activator PA28α/β or the immunoproteasome subunits LMP2 and LMP7 were used, the protective immunity against infection was profoundly attenuated. Our findings clearly demonstrate that vaccination with pGFP-TSA1 successfully induces protection dependent on CD8 + T cell activation, in which immunoproteasomes play a crucial role. It is noteworthy to document that physical binding of the epitope and GFP is required for induction of this protection, since mice vaccinated with pTSA1-IRES-GFP failed to acquire resistance, probably because the epitope and GFP are separately expressed in the antigen-presenting cells.
- Subjects :
- Protozoan Vaccines
Proteasome Endopeptidase Complex
Injections, Intradermal
Trypanosoma cruzi
T cell
Green Fluorescent Proteins
Immunology
Epitopes, T-Lymphocyte
CD8-Positive T-Lymphocytes
Lymphocyte Activation
Microbiology
Epitope
Green fluorescent protein
Major Histocompatibility Complex
Interferon-gamma
Mice
Multienzyme Complexes
T-Lymphocyte Subsets
Vaccines, DNA
medicine
Animals
Chagas Disease
Immunization Schedule
biology
Vaccination
Membrane Proteins
biology.organism_classification
Acquired immune system
Fusion protein
Virology
Molecular biology
Mice, Inbred C57BL
Cysteine Endopeptidases
Infectious Diseases
medicine.anatomical_structure
Female
CD8
Plasmids
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 12864579
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Microbes and Infection
- Accession number :
- edsair.doi.dedup.....39947fbcd73099636b03a9eebc8b9d5b