Subversion of effector CD8+ T cell differentiation in acute hepatitis C virus infection: exploring the immunological mechanisms

Hallmark of acute hepatitis C virus (HCV) infection is a severe virus-specific effector CD8(+) T cell dysfunction that seems to be a critical factor in preventing the resolution of infection and in favoring the onset of chronic liver immunopathology. We suggest that this dysfunction is critical in the establishment of HCV persistence, unless it is compensated by multispecific responses, as found in individuals resolving infection. Analyses on purified populations indicate that central memory HCV-specific CCR7(+)/CD8(+) T cells efficiently proliferate and differentiate in vitro, although the large population of memory effector CCR7(-) cells found in the peripheral blood of acutely infected patients display poor effector functions ex vivo (semi-effectors). However, we report strong evidence in support of IL-2 being capable of pushing semi-effector CTL to complete their effector cell program. Therefore, IL-2 deficiency during T cell activation may be responsible for the dichotomy between memory CTL expansion and incomplete effector differentiation shown in patients with acute HCV infection. These data are consistent with the possible therapeutic treatment with IL-2 to rebuild the effector T cell pool in these patients.     

Heat treatment modifies the allergenicity of beef and bovine serum albumin

The effect of heat on the allergenicity of beef and bovine serum albumin was investigated among 10 toddlers skin prick test (SPT)-positive to raw and cooked beef. The meat-allergy diagnosis was confirmed during double-blind, placebo-controlled food challenge (DBPCFC) with 180 g of beef cooked for 5 min at 100°C. SPT with homogenized and freeze-dried beef, and heated and unheated bovine serum albumin were performed. Both heated and unheated bovine serum albumin, homogenized beef, and freeze-dried beef were used in trial DBPCFC. All children were SPT-positive to unheated bovine serum albumin. Seven were positive to heated bovine serum albumin, one to freeze-dried beef, and none to homogenized beef. DBPCFCs were negative for homogenized beef and freeze-dried beef, positive for unheated bovine serum albumin in five patients, and positive for heated albumin in four children. We conclude that heating reduces sensitization to beef and bovine serum albumin but does not abolish reactivity to albumin under home conditions. However, industrially heat-treated and sterilized homogenized beef and freeze-dried beef may be suitable substitutes in beef-allergic children's diets.     

Serological survey of Toscana virus infections in a high-risk population in Italy

Toscana virus is the most important agent responsible for meningitis in central Italy. We report a serosurveillance study, using an immunoenzymatic assay, of 360 serum samples harvested from a high-risk population occupationally exposed to Toscana virus in two regions of Italy, Tuscany and Piedmont. The results indicates a seroprevalence of Toscana virus of 77.2% in the forestry workers, particularly in the Tuscany region. This fact is strictly correlated with the ecological niches specific for the survival of Toscana virus arthropod vector.     

Regulation of the chemokine system at the level of chemokine receptor expression and signaling activity

The chemokine system is highly influenced by the microenvironmental context. Regulation of the chemokine system occurs not only at the level of agonist production, but also at the level of chemokine receptor expression. This review provides examples of regulation of the system at the receptor level by modulation of receptor expression in canonical cellular targets (tuning of the system), and induction of novel receptors (shaping of the system), with particular attention to dendritic cells as a cellular model. Receptor signaling activity represents a further potential level of regulation of the system. Finally, chemokines can also influence the microenvironment by modulating gene expression in target cells.     

Familial mediterranean fever: The segregation of four different mutations in 13 individuals from one inbred family: Genotype–phenotype correlation and intrafamilial variability

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring attacks of fever and serositis. Six sequence alterations (M694V, V726A, K695R, M680I, M694I, and E148Q), in the MEFV gene, account for the majority of FMF chromosomes. Differences in the clinical expression have been mainly attributed to MEFV allelic heterogeneity. Homozygotes for the M694V mutation have a more severe form of the disease and more frequently demonstrate articular and renal complications. The clinical manifestations associated with mutation M680I are considered less severe. Mutations E148Q, K695R and V726A have reduced penetrance, and many individual homozygotes or compound heterozygotes for these mutations remain asymptomatic. Here we report on one inbred family with 13 individuals (one grandparent, three parents, and nine grandchildren), either homozygotes or compound heterozygotes, for one or two of four mutations (V726A, M694V, M680I, and K695R). Three parents and one grandparent who each carried two mutated alleles remained asymptomatic. Of nine grandchildren who were compound heterozygotes for two mutations in the MEFV gene, only those with either the M694V/V726A or the M694V/M680I genotypes manifested the disease, bearing further evidence to the severity of mutation M694V in individuals sharing a similar genetic and environmental background. Nevertheless, one father and one grandmother who carried the M694V/V726A compound heterozygous genotype were symptom‐free, while the four grandchildren with the same genotype manifested the disease from early age, providing further evidence for the role of additional environmental and genetic modifiers. The occurrence of four different mutations in two sets of consanguineous parents merits consideration per se. © 2002 Wiley‐Liss, Inc.     

HIV-1 subtypes and circulating recombinant forms (CRFs) from HIV-infected patients residing in two regions of central and southern Italy

A total of 347 pol gene sequences from 88 Tuscan and 259 Apulian subjects (including 52 non-Italians and 9 children) were analyzed phylogenetically. Forty-four (12.6%) non-B subtypes were found, including 3.4% C, 1.4% F1, 0.8% G, and 0.3% each for J and A pure subtypes, and 3.7% CRF02_AG, 1.4% CRF01_AE, 0.6% BF, and 0.3% CRF06-cpx recombinant forms. An additional sample close-matched the pol gene of an unique recombinant form (URF AGK 99GR303). The non-B subtypes were from 40 adults and 4 children; 12 of these 44 patients were epidemiologically linked. Thirty-three of the 44 non-B viruses pertained to non-Italian immigrants and 11 to Italians, signifying that 63.4% immigrants and 3.7% Italians harbored non-B subtypes. The overall frequency of non-B subtypes was higher in Tuscany than in Apulia (18.1% vs. 10.8%). Moreover, 6.1% and 3.0% non-B subtypes were found among Italians from Florence and Apulia, respectively, while 52.1% and 72.4% of immigrants living in Tuscany and Apulia harbored non-B subtypes. Women infected by means of sexual contact prevailed among non-Italian adults; the majority of Italians were males and admitted high-risk sexual behavior. Four Italians had a history of extensive travel in countries of high endemicity. Social and epidemiological changes are responsible for an increasing circulation of non-B subtypes in Italy. Although non-B subtypes principally infect non-Italian patients, in Italy they can no longer be considered exclusively restricted to subjects from endemic areas.