Chagas disease is a chronic infection caused by Trypanosoma cruzi, an intracellular protozoan parasite. Chronic chagasic patients (CCPs) have dysfunctional CD8+ T cells that are characterized by impaired cytokine production, high coexpression of inhibitory receptors, and advanced cellular differentiation. Most patients diagnosed in the chronic phase of Chagas disease already exhibit heart involvement, and there is no vaccination that protects against the disease. Antiparasitic treatment is controversial as to its indication for this stage of the disease. There is a lack of biological markers to evaluate the effectiveness of antiparasitic treatment, and little is known about the effect of the treatment on CD8+ T cells. Thus, the aim of the current study was to analyze the early effects of antiparasitic treatment on CD8+ T cells from CCPs with asymptomatic clinical forms of disease. To evaluate the CD8+ T cell subsets, expression of inhibitory receptors, and functionality of T cells in CCPs, PBMCs were isolated. The results showed that treatment of CCPs with the asymptomatic form of the disease induces an increase in the frequency of CD8+ central memory T cells and terminal effector T cells, a decrease in the coexpression of inhibitory receptors, an improved Ag-specific CD8+ T cell response exhibited by the individual production of IFN-γ or IL-2, and a multifunctional CD8+ T cell profile of up to four functions (IFN-γ+IL-2+Perforin+Granzyme B+). These findings suggest that, in CCPs, antiparasitic treatment improved the quality of Ag-specific CD8+ T cell responses associated with a decrease in inhibitory receptor coexpression, which could serve as biomarkers for monitoring the effectiveness of antiparasitic treatment.
This work was supported by the Vicerrectoría de Investigación from Pontificia Universidad Javeriana (Proposal 00006233 and Project 00006330) and by Grants SAF2013-48527-R and SAF2016-81003-R from the Programa Estatal Investigación, Desarrollo e Innovación of the Ministerio de Economía y Competitividad, the Red de Investigación Cooperativa en Enfermedades Tropicales (RD12/0018/0021 and RD12/0018/0018), and Fondo Europeo de Desarrollo Regional. J.M. was supported by Ph.D. studentships from the Departamento Administrativo de Ciencia, Tecnología e Inovación and Pontificia Universidad Javeriana.
The online version of this article contains supplemental material.
- Received December 12, 2016.
- Accepted February 7, 2017.
- Copyright © 2017 by The American Association of Immunologists, Inc.