The IL-23/T helper 17 (Th17) axis plays an important role in joint inflammation in ankylosing spondylitis (AS). Conventional CD4+ Th17 cells are a major source of IL-17A. IL-22 is another cytokine implicated in AS pathophysiology and is produced by Th17 and Th22 cells. In this study, we aimed to analyze conventional and non-conventional T cell subsets producing IL-17A and IL-22 in patients with AS. We thus evaluated the intracellular staining for IL-17A, IL-22, and IFN-γ in peripheral blood mononuclear cells of 36 patients with AS and 55 age- and sex-matched healthy controls (HC). Conventional CD4+ and CD8+ T cells, γδ T cells, and mucosal-associated invariant T (MAIT) cells were evaluated. In patients with AS, we found a decreased frequency and number of γδ T cells, of MAIT cells and of IFN-γ+ CD4+ and CD8+ T cells. Th17-related IL-17A+/IFN-γ− CD4+ T cells were decreased in AS. The number of IL-22+ MAIT cells was higher in AS compared with HC, as well as the number of IFN-γ+/IL-17A+ MAIT cells. The number of IFN-γ−/IL-17A+ MAIT cells was higher only in female patients with AS compared with female HC. The cellular source of IL-17A was thus not restricted to conventional Th17 CD4+ T cells and might involve innate-like T cells, such as MAIT cells. Circulating MAIT cells producing IL-22 were increased in AS. These results strengthen the importance of innate and innate-like sources of IL-17A and/or IL-22.
Memory verification is crucial for meaningful behavior. Orbitofrontal damage may impair verification and induce confabulation and inappropriate acts. The strategic retrieval account explains this state by deficient monitoring of memories' precise content, whereas the reality filter hypothesis explains it by a failure of an orbitofrontal mechanism suppressing the interference of memories that do not pertain to reality. The distinctiveness of these mechanisms has recently been questioned. Here, we juxtaposed these 2 mechanisms using high-resolution evoked potentials in healthy subjects who performed 2 runs of a continuous recognition task which contained pictures that precisely matched or only resembled previous pictures. We found behavioral and electrophysiological dissociation: Strategic content monitoring was maximally challenged by stimuli resembling previous ones, whereas reality filtering was maximally challenged by identical stimuli. Evoked potentials dissociated at 200-300 ms: Strategic monitoring induced a strong frontal negativity and a distinct cortical map configuration, which were particularly weakly expressed in reality filtering. Recognition of real repetitions was expressed at 300-400 ms, associated with ventromedial prefrontal activation. Thus, verification of a memory's concordance with the past (its content) dissociates from the verification of its concordance with the present. The role of these memory control mechanisms in the generation of confabulations and disorientation is discussed.
ABSTRACT:Diverse studies demonstrated that although immediately repeated stimuli are better and faster recognized than stimuli repeated after a delay, this comes at the price of less-efficient long-term retention. A recent-evoked potential study using source estimation of high-resolution scalp EEG indicated that while immediate repetition induced a strikingly different electrical activity than new items in the left-medial temporal lobe (MTL) after 200-300 ms, delayed repetition did not. In this study, we recorded evoked potentials in two epileptic patients with intracranial depth electrodes in diverse temporal and frontal areas as they performed the same task as in the previous study. We found that immediate repetition induced increase of neural activity specifically in the left MTL between 250 and 400 ms compared to new items and items repeated after a delay. The findings are important in two ways. First, they support our previous conclusion that novel information immediately initiates a consolidation process involving the left-hippocampal area, which remains vulnerable during active maintenance and increases its effectiveness during off-line processing. Second, they indicate that source estimation based on high-resolution scalp EEG correctly localizes the current source of electrical activity in midline structures like the MTL. V V C 2010 Wiley-Liss, Inc.
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