T Lymphocytes from Chagasic Patients Are Activated but Lack Proliferative Capacity and Down-Regulate CD28 and CD3ζ

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 cd3ζ 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 cd3ζ. 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 cd3ζ 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 cd3ζbright/cd3ζdim% ratios in cd4+ and cd8+ were lower in chagasic patients when compared with both control groups. the cd3ζbright/cd3ζdim% 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 cd3ζ. conclusions: cd8+ t lymphocytes from chagasic donors displayed reduced proliferative capacity,which might be associated with cd3ζ down-regulation and diminished cd28 expression on cd4 t cells. © 2013 giraldo et al.