It remains largely unclear how antigen-presenting cells (APCs) encounter effector or memory T cells efficiently in the periphery. Here we used a mouse contact hypersensitivity (CHS) model to show that upon epicutaneous antigen challenge, dendritic cells (DCs) formed clusters with effector T cells in dermal perivascular areas to promote in situ proliferation and activation of skin T cells in a manner dependent on antigen and the integrin LFA-1. We found that DCs accumulated in perivascular areas and that DC clustering was abrogated by depletion of macrophages. Treatment with interleukin 1α (IL-1α) induced production of the chemokine CXCL2 by dermal macrophages, and DC clustering was suppressed by blockade of either the receptor for IL-1 (IL-1R) or the receptor for CXCL2 (CXCR2). Our findings suggest that the dermal leukocyte cluster is an essential structure for elicitating acquired cutaneous immunity.
Delayed imaging that coincides with the highest uptake of fluorine-18 fluorodeoxyglucose (FDG) by tumour may be advantageous in oncological positron emission tomography (PET), where delineation of metastasis from normal tissue background is important. In order to identify the better imaging protocol for tumour detection, whole-body FDG-PET images acquired at 1 h and 2 h after injection were evaluated in 22 subjects, with a post-injection transmission scan at 90 min for attenuation correction. After visual interpretation, tumour uptake [tumour standardised uptake ratio (SUR)], normal tissue uptake (normal SUR) and tumour to background contrast (tumour SUR/normal tissue SUR) were evaluated in the images acquired at 1 h and at 2 h. Most malignant lesions, including primary lung cancer, metastatic mediastinal lymph nodes and lymphoma lesions, showed higher FDG uptake at 2 h than at 1 h. By contrast, benign lesions, with the exception of sarcoidosis, showed lower uptake of FDG at 2 h than at 1 h. Among normal tissues, the kidney, liver, mediastinum, lung, upper abdomen and left abdomen showed significant falls in FDG uptake from 1 h to 2 h. The lower abdomen, right abdomen and muscles (shoulder and thigh) showed no significant changes. Consequently, malignant lesions of the lung, mediastinum and upper abdomen showed significant increases in tumour to background contrast from 1 to 2 h. Three lesions (two lung cancers and a malignant lymphoma) that were equivocal on 1-h images became evident on 2-h images, changing the results of interpretation. All other malignant lesions were detected on 1-h images, but were clearer, with higher contrast, on 2-h images. Lesion-based sensitivity was improved from 92% (49/53) to 98% (52/53), and patient-based sensitivity from 78% (14/18) to 94% (17/18). It is concluded that delayed whole-body FDG-PET imaging is a better and more reliable imaging protocol for tumour detection.
The purpose of this study was to identify the functional fields activated in relation to the NO-GO decision. Nine healthy subjects participated in the study which consisted of two test positron emission tomography (PET) scans (GO/NO-GO task and response selection task) and one control scan. In the response selection task, subjects were asked to flex their thumb of the right hand when a light emitting diode (LED) placed 60 cm from their eyes turned on red and to flex their index finger of the right hand when LED turned on green. In the GO/NO-GO task, subjects were asked to flex their thumb when the LED turned on red, however, they were asked not to move their fingers when LED turned on green. In the control state, they were asked simply to look at the LED without any movement of finger during the course of the scan. The mean regional cerebral blood flow (rCBF) change images for each task minus control and task minus task were calculated and fields of significant rCBF changes were identified. Several fields in the prefrontal cortex of the right hemisphere were specifically activated in relation to the GO/NO-GO task. The results indicate that the prefrontal cortex of the right hemisphere may be a key structure to make a decision not to move.
Sawada et al. report that Resolvin E1 (RvE1) down-regulates DC motility in both steady state and inflammatory conditions in the skin and exerts its antiinflammatory effects in contact hypersensitivity. They propose the LTB4-BLT1 signaling blockade as a possible major mechanism through which RvE1 exerts its regulatory effects.
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