IL-7 unveils pathogen-specific T cells by enhancing antigen-recall responses

BACKGROUND: IL-7 promotes the generation, expansion and survival of memory T cells. Previous mouse and human studies showed that IL-7 can support immune cell reconstitution in lymphopenic conditions, expand tumor-reactive T cells for adoptive immunotherapy and enhance effector cytokine expression by autoreactive T cells. Whether pathogen-reactive T cells also benefit from IL-7 exposure remains unknown. METHODS: Here we investigated this issue in cultures of peripheral blood mononuclear cells (PBMCs) derived from patients infected with various endemic pathogens. After short-term exposure to IL-7, we measured PBMC responses to antigens (Ag) derived from pathogens, such as Mycobacterium tuberculosis (MTB), Candida albicans (Ca) and Cytomegalovirus (CMV), and to the superantigen Staphylococcus aureus enterotoxin B (SEB). RESULTS: We found that IL-7 favoured the expansion and, in some instances, the uncovering of pathogen-reactive CD4 T cells, by promoting pathogen-specific IFNɣ, IL-2 and TNF recall responses. CONCLUSIONS: Our findings indicate that IL-7 unveils and supports re-activation of pathogen-specific T cells with possible diagnostic, prognostic and therapeutic significance, of clinical value especially in conditions of pathogen persistence and chronic infectio

Virological pattern of hepatitis B infection in an HIV-positive man with fatal fulminant hepatitis B: a case report

<p>Abstract</p> <p>Introduction</p> <p>There seem to be no published data concerning the clinical impact of populations of hepatitis B virus (HBV) in the hepatic and extrahepatic compartments of HIV-infected people with severe acute hepatitis.</p> <p>Case presentation</p> <p>A 26-year-old Caucasian man presenting to our hospital with clinical symptoms suggesting acute hepatitis was found to have an acute hepatitis B profile upon admission. He developed fatal fulminant hepatitis and was found to be heavily immunocompromised due to HIV-1 infection. He had a high plasma HBV and HIV load, and analysis of the partial pre-S1/pre-S2 domain showed the presence of mixed infection with D and F genotypes. Analysis of the point mutations within this region revealed the presence of HBV strains with amino acid substitutions at the immunodominant epitopes involved in B or T cell recognition. A homogeneous population of a pre-core mutant strain harbouring the A1896G and A1899G affecting HBeAg expression was invariably found in the liver tissue, plasma and peripheral blood mononuclear cells despite active HBeAg secretion; it was the dominant strain in the liver only, and was characterised by the presence of two point mutations in the direct repeat 1 domain involved in HBV replication activity. Taken together, these mutations are indicative of a highly replicative virus capable of evading immune responses.</p> <p>Conclusion</p> <p>This case report provides clinical evidence of a possible association between the rapid spread of highly replicative escape mutants and the development of fulminant hepatitis in a heavily immunocompromised patient. Virological surveillance of severe acute hepatitis B may be important in establishing an early treatment strategy involving antiviral drugs capable of preventing liver failure, especially in individuals for whom liver transplantation is not accepted as a standard indication.</p

An In-House RD1-Based Enzyme-Linked Immunospot-Gamma Interferon Assay Instead of the Tuberculin Skin Test for Diagnosis of Latent Mycobacterium tuberculosis Infection

Identification of individuals infected with Mycobacterium tuberculosis is essential for the control of tuberculosis (TB). The specificity of the currently used tuberculin skin test (TST) is poor because of the broad antigenic cross-reactivity of purified protein derivative (PPD) with BCG vaccine strains and environmental mycobacteria. Both ESAT-6 and CFP-10, two secretory proteins that are highly specific for M. tuberculosis complex, elicit strong T-cell responses in subjects with TB. Using an enzyme-linked immunospot (ELISPOT)-IFN-γ assay and a restricted pool of peptides derived from ESAT-6 and CFP-10, we have previously demonstrated a high degree of specificity and sensitivity of the test for the diagnosis of TB. Here, 119 contacts of individuals with contagious TB who underwent TST and the ELISPOT-IFN-γ assay were consecutively recruited. We compared the efficacy of the two tests in detecting latent TB infection and defined a more appropriate TST cutoff point. There was little agreement between the tests (k = 0.33, P < 0.0001): 53% of the contacts with a positive TST were ELISPOT negative, and 7% with a negative TST were ELISPOT positive. Furthermore, respectively 76 and 59% of the ELISPOT-negative contacts responded in vitro to BCG and PPD, suggesting that most of them were BCG vaccinated or infected with nontuberculous mycobacteria. The number of spot-forming cells significantly correlated with TST induration (P < 0.0001). Our in-house ELISPOT assay based on a restricted pool of highly selected peptides is more accurate than TST for identifying individuals with latent TB infection and could improve chemoprophylaxis for the control of TB

Selected Pool of Peptides from ESAT-6 and CFP-10 Proteins for Detection of Mycobacterium tuberculosis Infection

We have validated a new test for detecting Mycobacterium tuberculosis infection. A pool of synthetic peptides derived from ESAT-6 and CFP-10 proteins was used to detect the number of specific gamma interferon-producing T cells by means of an enzyme-linked immunospot assay. Sixty-eight individuals positive for M. tuberculosis infection, either human immunodeficiency virus-seropositive or -seronegative, were studied. The test results were highly specific (87.5%) and sensitive (93.1%), more so than a classical lymphoproliferative assay (specificity and sensitivity of 77.27%), opening new possibilities for diagnosis and screening of tuberculosis. Moreover, the test allowed us to distinguish individuals infected with M. tuberculosis from those vaccinated with BCG

L’industria nei 150 anni dell’Unità d’Italia. Paradigmi e Protagonisti

“L’Industria nella costruzione dell’Italia Unita” è un tema cruciale sul quale la Fondazione Edisone l’Accademia Nazionale dei Lincei hanno promosso un convegno a Roma il 24 e 25 novembre 2011 per individuare quali siano stati i Protagonisti e i Paradigmi che hanno fatto dell’Italia uno dei più importanti Paesi industrializzati al mondo.Nello specifico il volume affronta la storia e il ruolo che nell’economia italiana hanno avuto settori cruciali come l’energia elettrica, gli idrocarburi, la chimica, la siderurgia, l’auto e, in generale, i principali comparti del made in Italy manifatturiero quali la meccanica, l’alimentare e la moda, nonché il design. In molti di questi settori l’Italia ha conseguito successi internazionali anche se in taluni ad una prima fase di importante sviluppo, è seguito un declino che ha danneggiato la competitività complessiva del sistema economico italiano. Per questo dall’analisi si possono anche ricavare delle indicazioni su quali siano le politiche al fine di accrescere la nostra competitività. Storia, attualità e politiche sono le tre tonalità di questo volume che si colloca opportunamente nelle celebrazioni dei 150 anni dell’Unità d’Italia spiegando come anche l’industria abbia svolto un ruolo di notevole rilevanza."Industry in the 150 years of the Italian Unity" is a crucial theme and was the subject of a meeting arranged by Fondazione Edison and the National Lincei Academy on 24th and 25th November 2011 with a view to identifying Protagonists and Paradigms that have been making Italy one of the major industrial countries in the world. The volume specifically addresses the history and the role played in the Italian economy by essential sectors such as electric energy, hydrocarbons, chemistry, steel industry, cars and, in general, the main areas of the Made-in-Italy manufacturing such as mechanics, food and fashion, as well as design. Italy has achieved international successes in many of these sectors, even though in some others the initial period of remarkable development was followed by a decline that has damaged the entire Italian economic system. For this reason indications may be found in our analysis about the necessary policies to improve our productivity. History, activities and politics are the three lines along which this volume celebrates the 150 years of Italy's Unity with a focus on the major role played by our industries

Altered distribution of natural killer cell subsets identified by CD56, CD27 and CD70 in primary and chronic human immunodeficiency virus-1 infection

Human natural killer (NK) (CD3− CD56+) cells can be divided into two functionally distinct subsets, CD3− CD56dim and CD3− CD56bright. We analysed the distribution of NK cell subsets in primary and chronic human immunodeficiency virus-1 (HIV-1) infection, to determine if HIV infection stage may influence the subset distribution. In primary infection, contrary to chronic infection, the CD3− CD56dim subset was expanded compared to healthy controls. We also studied the effect of antiretroviral therapy administered early in infection and found that NK cell subset distribution was partially restored after 6 months of antiretroviral therapy in primary infection, but not normalized. Recently, NK cells have been divided into CD27− and CD27+ subsets with different migratory and functional capacity and CD27-mediated NK cell activation has been described in mice. We therefore investigated whether CD27 and/or CD70 (CD27 ligand) expression on NK cells, and thus the distribution of these novel NK subsets, was altered in HIV-1-infected patients. We found up-regulated expression of both CD27 and CD70 on NK cells of patients, resulting in higher proportions of CD27high and CD70high NK cells, and this phenomenon was more pronounced in chronic infection. Experiments conducted in vitro suggest that the high interleukin-7 levels found during HIV-1 infection may participate in up-regulation of CD70 on NK cell subsets. Imbalance of NK cell subsets and up-regulated expression of CD27 and CD70 initiated early in HIV-1 infection may indicate NK cell activation and intrinsic defects initiated by HIV-1 to disarm the innate immune response to the virus