CD8low T cells expanded following acute Trypanosoma cruzi infection and benznidazole treatment are a relevant subset of IFN-γ producers.

Autor: Marins-Dos-Santos A; Laboratory on Thymus Research, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil., Olivieri BP; Laboratory for Innovations on Therapy, Education and Bioproducts, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil., Ferreira-Reis R; Laboratory on Thymus Research, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil., de Meis J; Laboratory on Thymus Research, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.; National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Rio de Janeiro, Brazil., Silva AA; Department of Pathology, School of Medicine, Federal Fluminense University, Niterói, Brazil., de Araújo-Jorge TC; Laboratory for Innovations on Therapy, Education and Bioproducts, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil., Lannes-Vieira J; Laboratory of Biology of the Interactions, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil., Cotta-de-Almeida V; Laboratory on Thymus Research, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.; National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Rio de Janeiro, Brazil.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2020 Dec 21; Vol. 14 (12), pp. e0008969. Date of Electronic Publication: 2020 Dec 21 (Print Publication: 2020).
DOI: 10.1371/journal.pntd.0008969
Abstrakt: CD8 T cells are regarded as pivotal players in both immunoprotection and immunopathology following Trypanosoma cruzi infection. Previously, we demonstrated the expansion of CD8+ T lymphocytes in the spleen of T. cruzi-infected mice under treatment with benznidazole (N-benzyl-2-nitroimidazole acetamide; Bz), a drug available for clinical therapy. This finding underlies the concept that the beneficial effects of Bz on controlling acute T. cruzi infection are related to a synergistic process between intrinsic trypanocidal effect and indirect triggering of the active immune response. In the present study, we particularly investigated the effect of Bz treatment on the CD8+ T cell subset following T. cruzi infection. Herein we demonstrated that, during acute T. cruzi infection, Bz treatment reduces and abbreviates the parasitemia, but maintains elevated expansion of CD8+ T cells. Within this subset, a remarkable group of CD8low cells was found in both Bz-treated and non-treated infected mice. In Bz-treated mice, early pathogen control paralleled the lower frequency of recently activated CD8low cells, as ascertained by CD69 expression. However, the CD8low subset sustains significant levels of CD44highCD62Llow and CD62LlowT-bethigh effector memory T cells, in both Bz-treated and non-treated infected mice. These CD8low cells also comprise the main group of spontaneous interferon (IFN)-γ-producing CD8+ T cells. Interestingly, following in vitro anti-CD3/CD28 stimulation, CD8+ T cells from Bz-treated T. cruzi-infected mice exhibited higher frequency of IFN-γ+ cells, which bear mostly a CD8low phenotype. Altogether, our results point to the marked presence of CD8low T cells that arise during acute T. cruzi infection, with Bz treatment promoting their significant expansion along with a potential effector program for high IFN-γ production.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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