Inhibitory Receptors Are Expressed by Trypanosoma cruzi-Specific Effector T Cells and in Hearts of Subjects with Chronic Chagas Disease

We had formerly demonstrated that subjects chronically infected with Trypanosoma cruzi show impaired T cell responses closely linked with a process of T cell exhaustion. Recently, the expression of several inhibitory receptors has been associated with T cell dysfunction and exhaustion. In this study, we have examined the expression of the cytotoxic T lymphocyte antigen 4 (CTLA-4) and the leukocyte immunoglobulin like receptor 1 (LIR-1) by peripheral T. cruzi antigen-responsive IFN-gamma (IFN-γ)-producing and total T cells from chronically T. cruzi-infected subjects with different clinical forms of the disease. CTAL-4 expression was also evaluated in heart tissue sections from subjects with severe myocarditis. The majority of IFN-γ-producing CD4+ T cells responsive to a parasite lysate preparation were found to express CTLA-4 but considerably lower frequencies express LIR-1, irrespective of the clinical status of the donor. Conversely, few IFN-γ-producing T cells responsive to tetanus and diphtheria toxoids expressed CTLA-4 and LIR-1. Polyclonal stimulation with anti-CD3 antibodies induced higher frequencies of CD4+CTAL-4+ T cells in patients with severe heart disease than in asymptomatic subjects. Ligation of CTLA-4 and LIR-1 with their agonistic antibodies, in vitro, reduces IFN-γ production. Conversely, CTLA-4 blockade did not improved IFN-γ production in response to T. cruzi antigens. Subjects with chronic T. cruzi infection had increased numbers of CD4+LIR-1+ among total peripheral blood mononuclear cells, relative to uninfected individuals and these numbers decreased after treatment with benznidazole. CTLA-4 was also expressed by CD3+ T lymphocytes infiltrating heart tissues from chronically infected subjects with severe myocarditis. These findings support the conclusion that persistent infection with T. cruzi leads to the upregulation of inhibitory receptors which could alter parasite specific T cell responses in the chronic phase of Chagas disease

Anti-collagenase, anti-elastase and anti-oxidant activities of extracts from 21 plants

BACKGROUND: Owing to their roles in tissue remodelling in health and disease, several studies have reported investigations on plant extracts as inhibitors of proteinases and as anti-oxidants. METHODS: The anti-ageing and anti-oxidant properties of 23 plant extracts (from 21 plant species) were assessed as anti-elastase and anti-collagenase activities and in selected anti-oxidant assays along with phenolic content. RESULTS: Anti-elastase activities were observed for nine of the extracts with inhibitory activity in the following order: white tea (approximately 89%), cleavers (approximately 58%), burdock root (approximately 51%), bladderwrack (approximately 50%), anise and angelica (approximately 32%). Anti-collagenase activities were exhibited by sixteen plants of which the highest activity was seen in white tea (approximately 87%), green tea (approximately 47%), rose tincture (approximately 41%), and lavender (approximately 31%). Nine plant extracts had activities against both elastase (E) and collagenase (C) and were ranked in the order of white tea (E:89%, C:87%) > bladderwrack (E:50%, C:25%) > cleavers (E:58%, C:7%) > rose tincture (E:22%, C:41%) > green tea (E:10%: C:47%) > rose aqueous (E: 24%, C:26%) > angelica (E:32%, C:17%) > anise (E:32%, C:6%) > pomegranate (E:15%, C:11%).Total phenolic content varied between 0.05 and 0.26 mg gallic acid equivalents (GAE)/mL with the exception of white tea (0.77 mg GAE/mL). For anti-oxidant assessment, the Trolox equivalent anti-oxidant capacity (TEAC) assay revealed activity for all extracts. White tea had the highest activity equivalent to approximately 21 microM Trolox for a 6.25 microg aliquot. In addition, seven extracts exhibited activities = 10 microM Trolox with witch hazel (6.25 microg = 13 microM Trolox) and rose aqueous (6.25 microg = 10 microM Trolox) showing very high activities at low concentrations. A high activity for white tea was also found in the superoxide dismutase (SOD) assay in which it exhibited ~88% inhibition of reduction of nitroblue tetrazolium. High activities were also observed for green tea (86.41%), rose tincture (82.77%), witch hazel (82.05%) and rose aqueous (73.86%). CONCLUSION: From a panel of twenty three plant extracts, some one dozen exhibit high or satisfactory anti-collagenase or anti-elastase activities, with nine having inhibitory activity against both enzymes. These included white tea which was found to have very high phenolic content, along with high TEAC and SOD activities

Electrically controlled light scattering from thermoreversible liquid-crystal gels

Thermoreversible gels of the liq.-crystal LC-E7 with 1,3:2,4-Di-O-benzylidene-D-sorbitol (DBS) form white light-scattering films that are reversibly switchable to a clear state by ac elec. fields. The light scattering by the gelled films is an intrinsic material property that originates in the phase diagram of the system displaying a monotectic-type equil. (\"mesotectic\") among a liq., a solid, and a mesophase at extremely low concns. of DBS. Electrooptical characteristics and demonstrated viscoelastic behavior of the films produced indicate the applicability of DBS/LC-E7 in large area scattering-based flat panel displays and projection systems. [on SciFinder (R)

CTLA-4 (CD152) expression in peripheral blood T cells in Kawasaki disease

Kawasaki disease (KD) is an acute febrile illness of early childhood caused by vasculitis. Whether or not peripheral blood T cells are activated in acute KD remains uncertain, as some reports have presented evidence of peripheral blood T cell activation, whereas others suggest that the level of peripheral blood T cell activation is low during acute KD. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, CD152) is a surface molecule of activated T cells. We therefore investigated intracellular CTLA-4 expression in the peripheral blood T cells of patients with acute KD as a marker of T cell activation. We collected blood samples from 20 patients with KD and six with Epstein–Barr virus infectious mononucleosis (EBV-IM) who were admitted to our hospital, as well as 13 healthy children. We determined the intracellular expression of CTLA-4 in T cells by flow cytometry. We demonstrated that the intracellular expression of CTLA-4 is up-regulated in peripheral blood CD3(+) T cells, CD4(+) T cells and CD8(+) T cells at the early part of the acute stage in KD. However, the mean percentages of intracellular T cells expressing CTLA-4 in EBV-IM patients were about fourfold higher than those in T cells from patients with acute KD. Our results suggested that the level of activation of peripheral blood T cells is very low during acute KD