Differential phenotypic and functional profile of epitope-specific cytotoxic CD8 + T cells in benznidazole-treated chronic asymptomatic Chagas disease patients

Biochim Biophys Acta Mol Basis Dis. 2020 Mar 1;1866(3):165629. doi: 10.1016/j.bbadis.2019.165629. Epub 2019 Dec 6.

Abstract

One of the greatest challenges in Chagas disease research is the search for tools that will enable the assessment of pharmacological treatment efficacy. A recently described set of serological biomarkers composed of four parasite antigens and established criteria of treatment efficacy allowed the evaluation of the impact of benznidazole treatment a short/medium time after the treatment. In addition, cellular immunological parameters have also been described as potential indicators of the treatment response. The cytotoxic CD8+ T cells specific to five epitopes in the PFR2, PFR3, TcCA-2 and KMP11 antigens have been analysed, and these epitopes have been shown to be recognized, processed and presented in the context of a natural T. cruzi infection. In the present manuscript, we characterized these antigen-specific CD8+ T cells in indeterminate chronic Chagas disease patients both before and after (from 11 to 28 months) benznidazole treatment. The results indicate that there is a differential memory CD8+ T cell profile depending on the antigenic epitope and that the benznidazole treatment modulates the memory, differentiation and senescence phenotypes of the epitope-specific CD8+ T cells. Moreover, in these patients, the reactivity of sera against the referred set of biomarkers was evaluated. The data obtained show that the patients who met the established therapeutic efficacy criteria presented a differential phenotypic profile of the antigen-specific CD8+ T cells even prior to treatment compared to the patients who did not meet the therapeutic efficacy criteria, and this behaviour is associated with a better functionality of these CD8+ T cells.

Keywords: Benznidazole treatment; Biomarkers; Chagas disease; Cytokines; Cytotoxic molecules; Epitope-specific CD8(+) T cells; Humoral response; Memory phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / parasitology
  • Chagas Disease / drug therapy*
  • Chagas Disease / immunology*
  • Chagas Disease / parasitology
  • Cytokines / immunology
  • Epitopes / immunology*
  • Female
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / parasitology
  • Male
  • Nitroimidazoles / therapeutic use*
  • Phenotype
  • Trypanosoma cruzi / drug effects
  • Trypanosoma cruzi / immunology

Substances

  • Biomarkers
  • Cytokines
  • Epitopes
  • Nitroimidazoles
  • benzonidazole