Please use this identifier to cite or link to this item:
Type
ArticleCopyright
Open access
Sustainable Development Goals
03 Saúde e Bem-EstarCollections
- IOC - Artigos de Periódicos [12819]
Metadata
Show full item record
RAPAMYCIN IMPROVES THE RESPONSE OF EFFECTOR AND MEMORY CD8+ T CELLS INDUCED BY IMMUNIZATION WITH ASP2 OF TRYPANOSOMA CRUZI
Vacina
Trypanosoma cruzi
Células T CD8+
mTOR
Célula T Effector CD8+
Memória CD8+ células T
mTOR
CD8+ T-cells
Vaccine
Trypanosoma cruzi
Effector CD8+ T cell
Memory CD8+ T cells
Author
Affilliation
Abstract
Deficiency in memory formation and increased immunosenescence are pivotal features of
Trypanosoma cruzi infection proposed to play a role in parasite persistence and disease
development. The vaccination protocol that consists in a prime with plasmid DNA followed
by the boost with a deficient recombinant human adenovirus type 5, both carrying the
ASP2 gene of T. cruzi, is a powerful strategy to elicit effector memory CD8+ T-cells against
this parasite. In virus infections, the inhibition of mTOR, a kinase involved in several
biological processes, improves the response of memory CD8+ T-cells. Therefore, our aim
was to assess the role of rapamycin, the pharmacological inhibitor of mTOR, in CD8+ T
response against T. cruzi induced by heterologous prime-boost vaccine. For this purpose,
C57BL/6 or A/Sn mice were immunized and daily treated with rapamycin for 34 days.
CD8+ T-cells response was evaluated by immunophenotyping, intracellular staining,
ELISpot assay and in vivo cytotoxicity. In comparison with vehicle-injection, rapamycin
administration during immunization enhanced the frequency of ASP2-specific CD8+ T cells and the percentage of the polyfunctional population, which degranulated (CD107a+
)
and secreted both interferon gamma (IFNg) and tumor necrosis factor (TNF). The beneficial
effects were long-lasting and could be detected 95 days after priming. Moreover, the
effects were detected in mice immunized with ten-fold lower doses of plasmid/adenovirus.
Additionally, the highly susceptible to T. cruzi infection A/Sn mice, when immunized with
low vaccine doses, treated with rapamycin, and challenged with trypomastigote forms of
the Y strain showed a survival rate of 100%, compared with 42% in vehicle-injected group.
Trying to shed light on the biological mechanisms involved in these beneficial effects on
CD8+ T-cells by mTOR inhibition after immunization, we showed that in vivo proliferation
was higher after rapamycin treatment compared with vehicle-injected group. Taken together, our data provide a new approach to vaccine development against intracellular
parasites, placing the mTOR inhibitor rapamycin as an adjuvant to improve effective CD8+
T-cell response.
Keywords in Portuguese
RapamicinaVacina
Trypanosoma cruzi
Células T CD8+
mTOR
Célula T Effector CD8+
Memória CD8+ células T
Keywords
RapamycinmTOR
CD8+ T-cells
Vaccine
Trypanosoma cruzi
Effector CD8+ T cell
Memory CD8+ T cells
Share