Direct Presentation Is Sufficient for an Efficient Anti-Viral CD8+ T Cell Response

The extent to which direct- and cross-presentation (DP and CP) contribute to the priming of CD8+ T cell (TCD8+) responses to viruses is unclear mainly because of the difficulty in separating the two processes. Hence, while CP in the absence of DP has been clearly demonstrated, induction of an anti-viral TCD8+ response that excludes CP has never been purposely shown. Using vaccinia virus (VACV), which has been used as the vaccine to rid the world of smallpox and is proposed as a vector for many other vaccines, we show that DP is the main mechanism for the priming of an anti-viral TCD8+ response. These findings provide important insights to our understanding of how one of the most effective anti-viral vaccines induces immunity and should contribute to the development of novel vaccines

Sonographic evaluation of the shoulder in asymptomatic elderly subjects with diabetes

<p>Abstract</p> <p>Background</p> <p>The prevalence of rotator cuff tears increases with age and several studies have shown that diabetes is associated with symptomatic shoulder pathologies. Aim of our research was to evaluate the prevalence of shoulder lesions in a population of asymptomatic elderly subjects, normal and with non insulin - dependent diabetes mellitus.</p> <p>Methods</p> <p>The study was performed on 48 subjects with diabetes and 32 controls (mean age: 71.5 ± 4.8 and 70.7 ± 4.5, respectively), who did not complain shoulder pain or dysfunction. An ultrasound examination was performed on both shoulders according to a standard protocol, utilizing multiplanar scans.</p> <p>Results</p> <p>Tendons thickness was greater in diabetics than in controls (Supraspinatus Tendon: 6.2 ± 0.09 mm <it>vs </it>5.2 ± 0.7 mm, p < 0.001; Biceps Tendon: 4 ± 0.8 mm <it>vs </it>3.2 ± 0.4 mm, p < 0.001). Sonographic appearances of degenerative features in the rotator cuff and biceps were more frequently observed in diabetics (Supraspinatus Tendon: 42.7% <it>vs </it>20.3%, p < 0.003; Biceps Tendon: 27% <it>vs </it>7.8%, p < 0.002).</p> <p>Subjects with diabetes exhibited more tears in the Supraspinatus Tendon (Minor tears: 15 (15.8%) <it>vs </it>2 (3.1%), p < 0.03; Major tears: 15 (15.8%) <it>vs </it>5 (7.8%), p = ns), but not in the long head of Biceps. More effusions in subacromial bursa were observed in diabetics (23.9% <it>vs </it>10.9%, p < 0.03) as well as tenosynovitis in biceps tendon (33.3% <it>vs </it>10.9%, p < 0.001).</p> <p>In both groups, pathological findings were prevalent on the dominant side, but no difference related to duration of diabetes was found.</p> <p>Conclusions</p> <p>Our results suggest that age - related rotator cuff tendon degenerative changes are more common in diabetics.</p> <p>Ultrasound is an useful tool for discovering in pre - symptomatic stages the subjects that may undergo shoulder symptomatic pathologies.</p

RAGE Expression in Human T Cells: A Link between Environmental Factors and Adaptive Immune Responses

The Receptor for Advanced Glycation Endproducts (RAGE) is a scavenger ligand that binds glycated endproducts as well as molecules released during cell death such as S100b and HMGB1. RAGE is expressed on antigen presenting cells where it may participate in activation of innate immune responses but its role in adaptive human immune responses has not been described. We have found that RAGE is expressed intracellularly in human T cells following TCR activation but constitutively on T cells from patients with diabetes. The levels of RAGE on T cells from patients with diabetes are not related to the level of glucose control. It co-localizes to the endosomes. Its expression increases in activated T cells from healthy control subjects but bystander cells also express RAGE after stimulation of the antigen specific T cells. RAGE ligands enhance RAGE expression. In patients with T1D, the level of RAGE expression decreases with T cell activation. RAGE+ T cells express higher levels of IL-17A, CD107a, and IL-5 than RAGE− cells from the same individual with T1D. Our studies have identified the expression of RAGE on adaptive immune cells and a role for this receptor and its ligands in modulating human immune responses

Commercial Nucleic-Acid Amplification Tests for Diagnosis of Pulmonary Tuberculosis in Respiratory Specimens: Meta-Analysis and Meta-Regression

BACKGROUND: Hundreds of studies have evaluated the diagnostic accuracy of nucleic-acid amplification tests (NAATs) for tuberculosis (TB). Commercial tests have been shown to give more consistent results than in-house assays. Previous meta-analyses have found high specificity but low and highly variable estimates of sensitivity. However, reasons for variability in study results have not been adequately explored. We performed a meta-analysis on the accuracy of commercial NAATs to diagnose pulmonary TB and meta-regression to identify factors that are associated with higher accuracy. METHODOLOGY/PRINCIPAL FINDINGS: We identified 2948 citations from searching the literature. We found 402 articles that met our eligibility criteria. In the final analysis, 125 separate studies from 105 articles that reported NAAT results from respiratory specimens were included. The pooled sensitivity was 0.85 (range 0.36-1.00) and the pooled specificity was 0.97 (range 0.54-1.00). However, both measures were significantly heterogeneous (p<.001). We performed subgroup and meta-regression analyses to identify sources of heterogeneity. Even after stratifying by type of commercial test, we could not account for the variability. In the meta-regression, the threshold effect was significant (p = .01) and the use of other respiratory specimens besides sputum was associated with higher accuracy. CONCLUSIONS/SIGNIFICANCE: The sensitivity and specificity estimates for commercial NAATs in respiratory specimens were highly variable, with sensitivity lower and more inconsistent than specificity. Thus, summary measures of diagnostic accuracy are not clinically meaningful. The use of different cut-off values and the use of specimens other than sputum could explain some of the observed heterogeneity. Based on these observations, commercial NAATs alone cannot be recommended to replace conventional tests for diagnosing pulmonary TB. Improvements in diagnostic accuracy, particularly sensitivity, need to be made in order for this expensive technology to be worthwhile and beneficial in low-resource countries