In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 15, No. 2 ( 2021-2-4), p. e0009059-
Abstract:
Signs of senescence and the late stages of differentiation associated with the more severe forms of Chagas disease have been described in the Trypanosoma cruzi antigen-specific CD4 + T-cell population. However, the mechanisms involved in these functions are not fully known. To date, little is known about the possible impact of benznidazole treatment on the T . cruzi -specific functional response of CD4 + T cells. Methodology/Principal findings The functional capacity of CD4 + T cells was analyzed by cytometric assays in chronic Chagas disease patients, with indeterminate form (IND) and cardiac alterations (CCC) (25 and 15, respectively) before and after benznidazole treatment. An increase in the multifunctional capacity (expression of IFN-γ, IL-2, TNF-α, perforin and/or granzyme B) of the antigen-specific CD4 + T cells was observed in indeterminate versus cardiac patients, which was associated with the reduced coexpression of inhibitory receptors (2B4, CD160, CTLA-4, PD-1 and/or TIM-3). The functional profile of these cells shows statistically significant differences between IND and CCC (p 〈 0.001), with a higher proportion of CD4 + T cells coexpressing 2 and 3 molecules in IND (54.4% versus 23.1% and 4.1% versus 2.4%, respectively). A significant decrease in the frequencies of CD4 + T cells that coexpress 2, 3 and 4 inhibitory receptors was observed in IND after 24–48 months of treatment (p 〈 0.05, p 〈 0.01 and p 〈 0.05, respectively), which was associated with an increase in antigen-specific multifunctional activity. The IND group showed, at 9–12 months after treatment, an increase in the CD4 + T cell subset coproducing three molecules, which were mainly granzyme B + , perforin + and IFN-γ + (1.4% versus 4.5%). Conclusions/Significance A CD4 + T cell dysfunctional process was detected in chronic Chagas disease patients, being more exacerbated in those patients with cardiac symptoms. After short-term benznidazole treatment (9–12 months), indeterminate patients showed a significant increase in the frequency of multifunctional antigen-specific CD4 + T cells.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0009059
DOI:
10.1371/journal.pntd.0009059.g001
DOI:
10.1371/journal.pntd.0009059.g002
DOI:
10.1371/journal.pntd.0009059.g003
DOI:
10.1371/journal.pntd.0009059.g004
DOI:
10.1371/journal.pntd.0009059.g005
DOI:
10.1371/journal.pntd.0009059.g006
DOI:
10.1371/journal.pntd.0009059.t001
DOI:
10.1371/journal.pntd.0009059.s001
DOI:
10.1371/journal.pntd.0009059.s002
DOI:
10.1371/journal.pntd.0009059.s003
DOI:
10.1371/journal.pntd.0009059.s004
DOI:
10.1371/journal.pntd.0009059.s005
DOI:
10.1371/journal.pntd.0009059.r001
DOI:
10.1371/journal.pntd.0009059.r002
DOI:
10.1371/journal.pntd.0009059.r003
DOI:
10.1371/journal.pntd.0009059.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2429704-5
Bookmarklink