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T lymphocytes from chagasic patients are activated but lack proliferative capacity and down-regulate CD28 and CD3?.


ABSTRACT:

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 CD3? 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 CD3?. 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 CD3? 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 CD3?(bright)/CD3?(dim)% ratios in CD4+ and CD8+ were lower in chagasic patients when compared with both control groups. The CD3?(bright)/CD3?(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 CD3?.

Conclusions

CD8+ T lymphocytes from chagasic donors displayed reduced proliferative capacity, which might be associated with CD3? down-regulation and diminished CD28 expression on CD4 T cells.

SUBMITTER: Giraldo NA 

PROVIDER: S-EPMC3561132 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

T lymphocytes from chagasic patients are activated but lack proliferative capacity and down-regulate CD28 and CD3ζ.

Giraldo Nicolás A NA   Bolaños Natalia I NI   Cuellar Adriana A   Roa Nubia N   Cucunubá Zulma Z   Rosas Fernando F   Velasco Víctor V   Puerta Concepción J CJ   González John M JM  

PLoS neglected tropical diseases 20130131 1


<h4>Background</h4>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 CD3ζ chain on T lymphocytes between chronic chagasic patients and uninfected controls.<h4>Methodology/principal findings</h4>Forty-two chronic chagasic patients, 28 healthy individuals and 32 non-chagasic cardiomyopathy donors were included. Peripheral blood was marked  ...[more]

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