Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells

The molecular events involved in the establishment and maintenance of CD4+ central memory and effector memory T cells (TCM and TEM, respectively) are poorly understood. In this study, we demonstrate that ex vivo isolated TCM are more resistant to both spontaneous and Fas-induced apoptosis than TEM and have an increased capacity to proliferate and persist in vitro. Using global gene expression profiling, single cell proteomics, and functional assays, we show that the survival of CD4+ TCM depends, at least in part, on the activation and phosphorylation of signal transducer and activator of transcription 5a (STAT5a) and forkhead box O3a (FOXO3a). TCM showed a significant increase in the levels of phosphorylation of STAT5a compared with TEM in response to both IL-2 (P < 0.04) and IL-7 (P < 0.002); the latter is well known for its capacity to enhance T cell survival. Moreover, ex vivo TCM express higher levels of the transcriptionally inactive phosphorylated forms of FOXO3a and concomitantly lower levels of the proapoptotic FOXO3a target, Bim. Experiments aimed at blocking FOXO3a phosphorylation confirmed the role of this phosphoprotein in protecting TCM from apoptosis. Our results provide, for the first time in humans, an insight into molecular mechanisms that could be responsible for the longevity and persistence of CD4+ TCM

High Visual Working Memory Capacity in Trait Social Anxiety

Working memory capacity is one of the most important cognitive functions influencing individual traits, such as attentional control, fluid intelligence, and also psychopathological traits. Previous research suggests that anxiety is associated with impaired cognitive function, and studies have shown low verbal working memory capacity in individuals with high trait anxiety. However, the relationship between trait anxiety and visual working memory capacity is still unclear. Considering that people allocate visual attention more widely to detect danger under threat, visual working memory capacity might be higher in anxious people. In the present study, we show that visual working memory capacity increases as trait social anxiety increases by using a change detection task. When the demand to inhibit distractors increased, however, high visual working memory capacity diminished in individuals with social anxiety, and instead, impaired filtering of distractors was predicted by trait social anxiety. State anxiety was not correlated with visual working memory capacity. These results indicate that socially anxious people could potentially hold a large amount of information in working memory. However, because of an impaired cognitive function, they could not inhibit goal-irrelevant distractors and their performance decreased under highly demanding conditions

Choking under monitoring pressure: being watched by the experimenter reduces executive attention

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