Proliferation requirements of cytomegalovirus-specific, effector-type human CD8+ T cells.

Two prototypic types of virus-specific CD8(+) T cells can be found in latently infected individuals: CD45R0(+)CD27(+)CCR7(-) effector-memory, and CD45RA(+)CD27(-)CCR7(-) effector-type cells. It has recently been implied that CD45RA(+)CD27(-)CCR7(-) T cells are terminally differentiated effector cells and as such have lost all proliferative capacity. We show in this study, however, that stimulation of CMV-specific CD45RA(+)CD27(-)CCR7(-) T cells with their cognate peptide in concert with either CD4(+) help or IL-2, IL-15, or IL-21 in fact induces massive clonal expansion. Concurrently, these stimulated effector T cells change cell surface phenotype from CD45RA to CD45R0 and regain CCR7, while effector functions are maintained. Our data imply that CD45RA(+)CD27(-)CCR7(-) effector-type T cells contribute to immunity not only by direct execution of effector functions, but also by yielding progeny in situations of viral reinfection or reactivation.

Absence of relationship between tuberculin reactivity and asthmatic symptoms, level of FEV1 and bronchial hyperresponsiveness in BCG vaccinated young adults.

BACKGROUND: Some recent studies have suggested that bacillus Calmette-Guérin (BCG) vaccination or mycobacterial infection early in life is inversely related to asthma. We wondered if an increase in tuberculin reactivity was inversely related to commonly used indices of asthma in a population of young adults who were BCG vaccinated at age 14. METHODS: Men and women aged 20-44 years, randomly selected from the general population, were tuberculin tested with the epinephrine-Pirquet method with Norwegian-produced synthetic medium tuberculin (n = 588). In addition they were interviewed using eight questions on asthma symptoms and medication. Lung function and bronchial responsiveness were also tested. RESULTS: Altogether 95% of those studied had been BCG vaccinated at age 14 (n = 558). In the 386 subjects with complete examinations, there was no relationship between a positive tuberculin reaction (> or = 4 mm) and asthma symptoms or use of asthma medication. Furthermore we did not observe any relationship between a positive tuberculin reaction and the level of forced expiratory volume (FEV1) or a positive bronchial responsiveness test, assessed as the percent of predicted of FEV1 and PD20 < 2 mg methacholine, respectively. In multiple logistic regression analyses neither respiratory symptoms, level of FEV1, nor bronchial hyperresponsiveness were related to tuberculin reactivity after adjustment for age, gender and smoking habits. CONCLUSIONS: In this young adult population who were BCG vaccinated at the age of 14 no significant relationship existed between tuberculin reactivity and asthmatic symptoms, level of FEV1 or bronchial hyperresponsiveness. Our data does not support the hypothesis that BCG immunization is beneficial in reducing asthmatic symptoms and disease in young adults.

Differential induction of apoptosis by virulent Mycobacterium tuberculosis in resistant and susceptible murine macrophages: role of nitric oxide and mycobacterial products.

Resistance and susceptibility of macrophages to mycobacteria are under the control of the Bcg/Nramp1 gene, which also controls the NO- production in response to macrophage activators. There is recent evidence indicating that mycobacteria induces apoptosis in infected macrophages. Using murine macrophage lines, congenic at the Bcg/Nramp1 gene, this report shows that B10R are more prone than B10S macrophages to undergo apoptosis after exposure to live virulent Mycobacterium tuberculosis H37Rv (Mtb) or PPD, as determined by cell viability, DNA fragmentation, hypoploidy, and the terminal deoxynucleotide transferase dUTP-biotin nick-end labeling assay. Induction of apoptosis correlated with NO- production. Aminoguanidine and anti-TNF-alpha inhibited NO- production and apoptosis. B10R and B10S macrophages were equally affected by sodium nitroprusside, a donor of NO-, but its effect, mainly in B10R cells, was enhanced by the presence of Mtb. Nonvirulent mycobacteria induced lower levels of NO- and did not cause cell death. Killed Mtb, mannose-capped lipoarabinomannan (ManLAM), and LPS rescued macrophages from apoptosis albeit induce NO-. These findings suggest the existence of opposite pathways: metabolically active mycobacteria promotes apoptosis whereas their structural components inhibit it. Apoptosis may be a critical mechanism by which Nramp1 gene controls the macrophage infection with virulent mycobacteria.

Proliferation of peripheral blood mononuclear cells from rheumatoid arthritis patients to mycobacterial antigens.

Proliferation of rheumatoid and control peripheral blood mononuclear cells (PBMC) to an antigenic acetone-precipitable extract from mycobacterium tuberculosis (MTa) was investigated. Cells were also stimulated with the recall antigen tuberculin PPD (purified protein derivative) and the mitogen OKT3. Controls had a significantly higher response to both MTa and tuberculin PPD than RA patients. However, lymphocytes from patients who had had their disease for 3-10 years proliferated more vigorously to MTa than did PBMD from patients with longer disease duration. There was no difference in the proliferation to OKT3 between patients and controls. We were not able to confirm a previously found correlation between the HLA-DR4 phenotype and lymphocyte transformation to MTa.

Correlação tuberculina-lepromina / Correlation tuberculin-lepromin

There existe no mutual relation between positiveness to Mantoux test and to that of Mitsuda among lepromatous patients. This fact constitutes, just like many others in the field of leprosy, an open question to further investigations.