Double Positive CD4+CD8+ (DP) T-Cells Display Distinct Exhaustion Phenotype in Chronic Hepatitis C.

In chronic hepatitis C (CHC), characterized by exhaustion of T-cell function, increased frequencies of double-positive (DP) (CD4+CD8+) cells are present in peripheral blood. We compared the exhaustion phenotype between DP and single positive (SP) T-cells, including HCV-specific cells, and assessed the effect of successful HCV treatment on inhibitory receptors expression. Blood samples from 97 CHC patients were collected before and six months post-treatment. PD-1 (programmed cell death protein 1) and Tim-3 (T-cell immunoglobulin and mucin domain-containing molecule-3) expression was assessed by flow cytometry. DP T-cells displayed significantly higher PD-1 expression, lower Tim-3 expression than CD8+ SP T-cells and lower percentages of PD-1-Tim-3- cells than CD4+ SP T-cells, both before and after treatment. PD-1+Tim-3+ DP T-cells decreased following treatment. HCV-specific cells were more frequent among DP than SP T-cells, both before and after treatment. HCV-specific DP T-cells were characterized by lower PD-1 expression, higher PD-1 and Tim-3 co-expression, and lower percentages of PD-1-Tim-3- cells (both before and after treatment) and higher post-treatment Tim-3 than HCV-specific SP T-cells. Their percentages decreased following treatment, but the exhaustion phenotype remained unchanged. DP T-cells in CHC exhibit a distinct exhaustion phenotype from SP T-cells, and these changes mostly persist following successful treatment.

Graphene oxide as a new anthropogenic stress factor - multigenerational study at the molecular, cellular, individual and population level of Acheta domesticus.

Although interest in transgenerational phenomena is constantly growing, little is known about the long-term toxicity of nanoparticles. In this study we investigate the multigenerational effects of graphene oxide (GO) which was given to Acheta domesticus in low doses (0.2, 2 and 20 µg·g-1 of food) for three subsequent generations. We assessed the influence of GO nanoparticles in many contexts, basing on parameters which represented different levels of biological organization: activity of antioxidant enzymes, level of apoptosis, DNA damage, histological analysis, hatching abilities, body mass and body length of insects, as well as their survival rate. The results have shown that exposing insects to nanoparticles over an extended period of time causes surprising intergenerational effects, based on significant differences in the life cycle and reproductive processes, which are not always dose-dependent. The second generation of insects appeared as the most unstable among the parameters that were studied, and did not match trends and patterns in the first and third generation categories. An increase of DNA damage was observed, but only in the third generation. This reduction of genome stability can be perceived as an essential element of adaptation, leading to an increase of genotype variants, which then undergo selection.