Influenza virus specific CD8⁺ T cells exacerbate infection following high dose influenza challenge of aged mice.

Influenza viruses cause severe illnesses and death, mainly in the aged population. Protection afforded by licensed vaccines through subtype-specific neutralizing antibodies is incomplete, especially when the vaccine antigens fail to closely match those of the circulating viral strains. Efforts are underway to generate a so-called universal influenza vaccine expressing conserved viral sequences that induce broad protection to multiple strains of influenza virus through the induction of CD8⁺ T cells. Here we assess the effect of a potent antiviral CD8⁺ T cell response on influenza virus infection of young and aged mice. Our results show that CD8⁺ T cell-inducing vaccines can provide some protection to young mice, but they exacerbate influenza virus-associated disease in aged mice, causing extensive lung pathology and death.

Human dentin matrix induces cartilage formation in vitro by mesenchymal cells derived from embryonic muscle.

Dentin matrix was assayed for its potential to elicit chondrogenesis of mesenchymal cells in vitro. The substratum was prepared by demineralization of human tooth root dentin, while embryonic thigh muscle was used as a source of mesenchymal cells. Formation of chondrocytes from mesenchymal cells occurred in the presence of dentin matrix, and in the same sequence as previously shown with substrata of demineralized bone.

False positivity of Legionella serology in patients with cystic fibrosis.

Respiratory deterioration accounts for the morbidity and mortality observed in patients with cystic fibrosis. The role of Legionella in this deterioration was determined in a 2-year prospective study of 49 patients with cystic fibrosis and 19 sibling controls. Sera were obtained from participants on enrollment and at quarterly intervals. Legionella antibodies were measured in parallel using an indirect fluorescent assay. No seroconversions were observed. Eleven of 49 patients with cystic fibrosis (22%) were seropositive compared to none of 19 siblings (P less than 0.05). Six of the 11 patients demonstrated high titers (greater than or equal to 1:512) that persisted throughout the study. Absorption with pools of various Pseudomonas species reduced the antibody titers such that only 3 remained positive after absorption. Legionella was not found to be an important cause of clinical deterioration during this study. The results of the absorption studies suggest that high titers to Legionella in this population are due to cross-reacting antibodies.

Association of respiratory viral infections with pulmonary deterioration in patients with cystic fibrosis.

In a two-year prospective study, we examined the effect of respiratory viral infections on pulmonary function in 49 patients with cystic fibrosis (mean age, 13.7 years). Nineteen normal siblings (mean age, 14) served as controls. Subjects were assessed quarterly and at the time of any respiratory illness. Each assessment included nasal washes for viral isolation and blood drawing for respiratory viral serologic studies. Pulmonary-function tests were performed at least twice yearly. Respiratory illnesses were reported significantly more often in the patients (3.7 per year) than in the normal siblings (1.7 per year), although the frequency of proved viral infections (1.67 per year) was identical. In the patients with cystic fibrosis significant correlations (P less than 0.0001) were found between the annual incidence of viral infections and every measure of disease progression in the two-year period, including the rate of decline of the Shwachman score (r = 0.71), the percentage of ideal weight for height (r = 0.80), the forced vital capacity (r = 0.85), the forced expiratory volume in the first second (r = 0.84), the forced midexpiratory flow rate (r = 0.68), and the frequency (r = 0.53) and duration (r = 0.84) of hospitalizations for respiratory exacerbations. We conclude that frequency of viral respiratory infections is closely associated with pulmonary deterioration in patients with cystic fibrosis.