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Title

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

AuthorsEgui, Adriana; López López, Manuel Carlos; Gómez, I.; Simón, M.; Segovia, M.; Thomas, María del Carmen
Issue Date2020
PublisherElsevier
CitationBiochimica et Biophysica Acta - Molecular Basis of Disease 1866 (2020)
AbstractOne 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.
Publisher version (URL)http://dx.doi.org/10.1016/j.bbadis.2019.165629
URIhttp://hdl.handle.net/10261/213966
DOIhttp://dx.doi.org/10.1016/j.bbadis.2019.165629
Identifiersdoi: 10.1016/j.bbadis.2019.165629
issn: 0925-4439
e-issn: 1879-260X
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