Inhibition of anti-CD3 monoclonal antibody-induced T-cell proliferation by dexamethosone,isoproterenol, or prostaglandin E2 either alone or in combination

1. The purpose of these studies was to investigate the modulation of the proliferation of human T cells obtained from peripheral blood by dexamethasone (DEX), isoproterenol (ISO), and prostaglandin E2 (PGE2). The former two substances interact with T cells via the glucocorticoid and beta-adrenergic receptors respectively. When occupied by their natural ligands, glucocorticosteroids and catecholamines, these receptors have a role in modulating T-cell function during stress. During the inflammatory response increased levels of PGE2 bind to their receptors on T cells and thus alter responsiveness. Proliferation of T cells was induced by immobilized anti-CD3 monoclonal antibody (mAb) in the presence or absence of an additional costimulatory signal delivered by anti-CD28 mAb. 2. Various physiologic concentrations of DEX, ISO, or PGE2 were added at the time of initiation of the cultures and subsequent proliferation of the unstimulated T cells was determined. The results demonstrate that physiologic concentrations of all three of these agents inhibit the anti-CD3 mAb-induced proliferation of T cells. 3. Although DEX and PGE2 were equipotent in suppressing T-cell proliferation, ISO was much less effective. 4. Because concomitant elevations in the peripheral levels of these substances may occur, experiments were performed to determine the T-cell inhibitory effects of DEX together with either PGE2 or ISO. Synergistic suppression of T-cell proliferation was observed when various concentrations of DEX and PGE2, but not DEX and ISO, were added to cultures. This synergistic suppression could not be explained by an increase in cAMP accumulation in T cells stimulated with DEX and PGE2. 5. Finally, the addition of anti-CD28 mAb to anti-CD3 mAb-stimulated T cells overcame much of the suppression of proliferation induced by PGE2 or ISO but less so than that induced by DEX.     

Polar Characterization of Antifungal Peptides from APD2 Database

The increase in the number of pathogens due to fungi that are tolerant to therapies does not grow at the same speed than the advance on new antifungal drugs. In this sense, it is imperative to find anti-fungi peptides that are not detrimental to mammalian cells and have an effective toxicity to fungi. In this work, we use a method called polarity index, to identify anti-fungi peptides with an efficiency of 70 %. This method already published, initially identified selective antibacterial peptides from APD2 Database, and was characterized by developing a comprehensive analysis of the polar dynamics of a peptide from its linear sequence. Discriminating tests showed that in addition to being efficient in this identification, it was also good at rejecting other classifications of peptides found in that same database.