T lymphocytes from chagasic patients are activated but lack proliferative capacity and down-regulate CD28 and CD3θ

Background: Chronic persistent infections have been associated with T lymphocytes functional impairment. The aim of this study was to compare the activation status, the proliferative potential and the expression of CD28 and CD3θ chain on T lymphocytes between chronic chagasic patients and uninfected controls. Methodology/Principal Findings: Forty-two chronic chagasic patients, 28 healthy individuals and 32 non-chagasic cardiomyopathy donors were included. Peripheral blood was marked for CD3, CD4, CD8, HLA-DR, CD28, CD38 and intracellular CD3θ. Peripheral blood mononuclear cells were stained with carboxyfluorescein diacetate succinimidylester and incubated with T. cruzi lysate or phytohemagglutinin for five days. Cells from 3 healthy controls were incubated with T. cruzi trypomastigotes separated with transwells; and the expression of CD3θ chain and proliferation index was determined. Heart-infiltrating cells from two chronic chagasic patients were tested for the aforementioned cellular markers. Chagasic patients displayed higher frequencies of CD4+/HLA-DR+/CD38+ (8.1% ± 6.1) and CD8+/HLA-DR+/CD38+ (19.8 ± 8.9) T cells in comparison with healthy (1.6 ± 1.0;10.6 ± 8.0) and non-chagasic cardiomyopathy donors (2.9 ± 2.9;5.8 ± 6.8). Furthermore, the percentage of CD4+ activated T cells was higher in chagasic patients with cardiac involvement. CD8+ T cells proliferation index in chagasic donors (1.7 ± 0.3) was lower when compared with healthy (2.3 ± 0.3) and non-chagasic cardiomyopathy individuals (3.1 ± 1.1). The frequencies of CD4+/CD28+ and CD8+/CD28+ T cells, as well as the [CD3θ.sup.bright]/[CD3θ.sup.dim]% ratios in CD4+ and CD8+ were lower in chagasic patients when compared with both control groups. The [CD3θ.sup.bright]/[CD3θ.sup.dim]% ratio and proliferative indexes for CD4+ and CD8+ T lymphocytes decreased gradually in those cells cultivated with parasites and displayed lower values than those incubated with medium alone. Finally, heart-infiltrating T cells from two T. cruzi infected patients also expressed activation markers and down-regulate CD28 and CD3θ. Conclusions: CD8+ T lymphocytes from chagasic donors displayed reduced proliferative capacity, which might be associated with CD3θ down-regulation and diminished CD28 expression on CD4 T cells.