CD4-CD8-αß and γδ T cells display inflammatory and regulatory potentials during human tuberculosis.

T-cells play an important role controlling immunity against pathogens and therefore influence the outcome of human diseases. Although most T-lymphocytes co-express either CD4 or CD8, a smaller T-cell subset found the in the human peripheral blood that expresses the αß or γδ T-cell-receptor (TCR) lacks the CD4 and CD8 co-receptors. These double negative (DN) T-cells have been shown to display important immunological functions in human diseases. To better understand the role of DN T-cells in human Mycobacterium tuberculosis, we have characterized their frequency, activation and cytokine profile in a well-defined group of tuberculosis patients, categorized as severe and non-severe based on their clinical status. Our data showed that whereas high frequency of αß DN T-cells observed in M. tuberculosis-infected patients are associated with disease severity, decreased proportion of γδ DN T-cells are found in patients with severe tuberculosis. Together with activation of CD4(+) and CD8(+) T-cells, higher frequencies of both αß and γδ DN T-cells from tuberculosis patients also express the chronic activation marker HLA-DR. However, the expression of CD69, an early activation marker, is selectively observed in DN T-cells. Interestingly, while αß and γδ DN T-cells from patients with non-severe tuberculosis display a pro-inflammatory cytokine profile, characterized by enhanced IFN-γ, the γδ DN T-cells from patients with severe disease express a modulatory profile exemplified by enhanced interleukin-10 production. Overall, our findings suggest that αß and γδ DN T-cell present disparate immunoregulatory potentials and seems to contribute to the development/maintenance of distinct clinical aspects of TB, as part of the complex immunological network triggered by the TB infection.

Evaluation of the immunotoxicological effects of Dimorphandra mollis Benth., Fabaceae, in rats / Avaliação dos efetos imunotoxicológicos de Dimorphandra mollis Benth., Fabaceae, em ratos

Dimorphandra mollis Benth., Fabaceae, also known as "faveira" or "fava-d'anta", is a plant common to the central woodsy meadow region of Brazil. It is well known for its antioxidant, antiplatelet and, principally, vasoprotective properties. Its principal component is rutin. The objective of this study is the evaluation of the safety of the use of the dried D. mollis extract in rodents. The rutin content of the standardized extract was 76.0±3 percent. With respect to the biochemical and hematological parameters evaluated, no alterations in the groups of rats that received 1000 and 2000 mg/kg doses of D. mollis were observed, but an increase in eosinophiles occurred. Hyperactivity of the white splenic pulp was detected in the group that received the 2000 mg/kg dose of D. mollis. In the evaluation of the lymphproliferative response with 1000 and 2000 mg/kg, no alterations were observed, and a decrease in IgG was only observed in the studies with a 2000 mg/kg dose. The results obtained with rodents suggest that no toxicity exists with the administration of dried D. mollis extract in a 1000 mg/kg dose.

A Dimorphandra mollis Benth., Fabaceae, conhecida como faveira ou fava-d'anta, é uma planta comum do cerrado central do Brasil, muito utilizada por suas propriedades antioxidante, antiplaquetária e, principalmente, como vasoprotetora. Seu principal marcador é a rutina. Este estudo teve como objetivo avaliar a segurança da utilização do extrato seco de D. mollis em roedores. O extrato foi extraído, padronizado e quantificado apresentando teor de 76,0±3 por cento de rutina. Nos parâmetros bioquímicos e hematológicos avaliados, não se observou alterações nos grupos de machos e fêmeas que receberam a dose de 1000 e 2000 mg/kg de D. mollis, mas observou-se um aumento de eosinófilos. Nos estudos histopatológicos detectou-se hiperreatividade da polpa branca esplênica, no grupo que recebeu a dose de 2000 mg/kg de D. mollis. Na avaliação da resposta linfoproliferativa, com 1000 e 2000 mg/kg não foram observadas alterações, e somente nos estudos com a dose de 2000 mg/kg se observou diminuição de IgG. Os resultados obtidos, utilizando roedores, sugerem que nenhuma toxicidade existe na administração de extrato seco de D. mollis na dose de 1000 mg/kg.

Physicochemical characterization and study of in vitro interactions of pH-sensitive liposomes with the complement system.

Complement activation is an important step in the acceleration of liposome clearance. The anaphylatoxins released following complement activation may motivate a wide variety of physiologic changes. We performed physicochemical characterization and in vitro studies of the interaction of complement system with both noncirculating and long-circulating pH-sensitive and nonpH-sensitive liposomes. The liposomes were characterized by diameter, zeta potential, and atomic force microscopy (AFM). The study of liposome interactions with complement system was conducted using hemolytic assay in rat serum. All liposomes presented a similar mean diameter (between 99.8 and 124.3 nm). The zeta potential was negative in all liposome preparations, except in liposomes modified with aminopoly (ethyleneglycol) 2000-distearoylphosphatidylethanolamine (aPEG(2000)-DSPE), which presented positive zeta potential. Atomic force microscopy images showed that non-long-circulating pH-sensitive liposomes are prone to vesicles aggregation. Non-pH-sensitive liposomes complement system activates, while pH-sensitive liposomes showed to be poor complement activators in rat serum.