Selective Impairment of TH17-Differentiation and Protection against Autoimmune Arthritis after Overexpression of BCL2A1 in T Lymphocytes.

The inhibition of apoptotic cell death in T cells through the dysregulated expression of BCL2 family members has been associated with the protection against the development of different autoimmune diseases. However, multiple mechanisms were proposed to be responsible for such protective effect. The purpose of this study was to explore the effect of the T-cell overexpression of BCL2A1, an anti-apoptotic BCL2 family member without an effect on cell cycle progression, in the development of collagen-induced arthritis.

Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor, a Transforming Growth Factor β Rheostat That Controls Murine Treg Cell/Th17 Cell Differentiation and the Development of Autoimmune Arthritis by Reducing Interleukin-2 Signaling.

Objective: Transforming growth factor β (TGFβ) plays a prominent role in the establishment of immunologic tolerance, and mice lacking TGFβ1 die of multiorgan inflammation early in life. TGFβ controls the differentiation of CD4+ lymphocytes into Treg cells or proinflammatory Th17 cells. Although this dual capacity is modulated by the presence of additional cytokines around the activated cells, TGFβ also dissociates Th17/Treg cell differentiation in a dose-dependent manner by mechanisms still unknown.

Distinct serum proteome profiles associated with collagen-induced arthritis and complete Freund's adjuvant-induced inflammation in CD38⁻/⁻ mice: The discriminative power of protein species or proteoforms.

Collagen-type-II-induced arthritis (CIA) is an autoimmune disease, which involves a complex host systemic response including inflammatory and autoimmune reactions. CIA is milder in CD38(-/-) than in wild-type (WT) mice. ProteoMiner-equalized serum samples were subjected to 2D-DiGE and MS-MALDI-TOF/TOF analyses to identify proteins that changed in their relative abundances in CD38(-/-) versus WT mice either with arthritis (CIA(+) ), with no arthritis (CIA(-) ), or with inflammation (complete Freund's adjuvant (CFA)-treated mice).

Appraisal of snakebite incidence and mortality in Bolivia.

No information has been yet published on snakebite in Bolivia. The country includes very different ecological situations leading to various epidemiological risks. A study has been carried out to evaluate the incidence and location of snakebite, particularly in relation with altitude, in order to improve management.

Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses.

CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on thymocytes and mature T and B1a lymphocytes. Current data support the view that CD5 is a negative regulator of antigen-specific receptor-mediated signaling in these cells, and that this would likely be achieved through interaction with CD5 ligand/s (CD5L) of still undefined nature expressed on immune or accessory cells. To determine the functional consequence of loss of CD5/CD5L interaction in vivo, a new transgenic mouse line was generated (shCD5EμTg), expressing a circulating soluble form of human CD5 (shCD5) as a decoy to impair membrane-bound CD5 function.

Evaluation of compliance to congenital Chagas disease treatment: results of a randomised trial in Bolivia.

Background: A randomised, unblinded, clinical trial comparing two benznidazole regimens for congenital Chagas disease was carried out to determine whether simplification and reduction in the length of treatment could lead to better treatment compliance.

Methods: This study was conducted in Santa Cruz, Bolivia. Serological screening was carried out in pregnant women, and parasites were sought in the blood of newborns from seropositive mothers.

p27(Kip1) inhibits systemic autoimmunity through the control of Treg cell activity and differentiation.

Objective: Despite the importance of Treg cells in the maintenance of immunologic tolerance, the mechanisms that control their generation and activity are unknown. Since the cell cycle inhibitor p27(Kip1) (p27) was involved in T cell anergy, we undertook this study to explore its role in both Treg cell processes.

Methods: The development of type II collagen-induced arthritis (CIA) and lupus-like abnormalities was compared between transgenic mice overexpressing human Bcl-2 in T cells (BCL2-TgT mice) and nontransgenic mice that were deficient or not deficient in p27.

Mice deficient in CD38 develop an attenuated form of collagen type II-induced arthritis.

CD38, a type II transmembrane glycoprotein expressed in many cells of the immune system, is involved in cell signaling, migration and differentiation. Studies in CD38 deficient mice (CD38 KO mice) indicate that this molecule controls inflammatory immune responses, although its involvement in these responses depends on the disease model analyzed. Here, we explored the role of CD38 in the control of autoimmune responses using chicken collagen type II (col II) immunized C57BL/6-CD38 KO mice as a model of collagen-induced arthritis (CIA).

Influence of pregnancy on Trypanosoma cruzi parasitemia in chronically infected women in a rural Bolivian community.

To determine the role of pregnancy on Trypanosoma cruzi parasitemia, a matched cohort study was carried out in a rural Bolivian community comparing parasite rates in gravidae, puerperae, and non-pregnant infected women. A selection of 67 chronically infected women, who delivered between March 2004 and May 2005, were initially evaluated during the third trimester of pregnancy and again after delivery. They were matched for age, parity, and location with 104 seropositive non-pregnant women, who likewise had submitted blood for microscopic examination for T.

Door-to-door screening as a strategy for the detection of congenital Chagas disease in rural Bolivia.

Objective: To demonstrate the feasibility of a house-to-house screening system used for congenital Chagas disease in rural areas based on an active search for pregnant women and newborns in their homes in addition to passive case detection in health facilities.

Methods: Exploratory phase conducted by the research team followed by an operational period coordinated by municipal health service. A blood sample was taken for serological and parasitological tests of Trypanosoma cruzi from pregnant women who were searching antenatal care or visited at home by field investigators.

Exacerbation of type II collagen-induced arthritis in apolipoprotein E-deficient mice in association with the expansion of Th1 and Th17 cells.

Objective: To explore the bidirectional relationship between the development of rheumatoid arthritis (RA) and atherosclerosis using bovine type II collagen (CII)-immunized B10.RIII apoE(-/-) mice, a murine model of spontaneous atherosclerosis and collagen-induced arthritis (CIA).

Methods: Male B10.

GITR contributes to the systemic adjuvanticity of the Escherichia coli heat-labile enterotoxin.

The Escherichia coli heat-labile enterotoxin (LT) possesses a powerful mucosal and systemic adjuvant effect. However, little is known about the cellular and molecular basis of the immunostimulatory activity of LT at the mucosal level, and even less information is available on the mechanisms underlying its systemic adjuvant activity. In this study, we show that distinct mechanisms are responsible for the parenteral and mucosal adjuvanticity of LT.

Antibody drop in newborns congenitally infected by Trypanosoma cruzi treated with benznidazole.

Objective: To compare the drop of Chagas antibody titres between non-infected and congenitally infected newborns treated by two doses of benznidazole, aiming at evaluating the recovery time and giving recommendations regarding serological criteria of recovery.

Methods: During a clinical trial, the drop of Trypanosoma cruzi antibody titres measured by ELISA tests was followed during the first year of life in congenitally infected newborns treated with different doses of benznidazole and compared to T. cruzi antibody titres in non-parasitaemic newborns.

Sensitivity and specificity of Chagas Stat-Pak test in Bolivia.

Objective: To compare the results of an immunochromatographic test performed on whole blood, Chagas Stat-Pak, with those of an ELISA test using recombinant antigens.

Method: We tested 995 subjects of a rural population of all ages in the south of Bolivia, 459 pregnant women of the same population and 1030 urban women giving birth from the east of Bolivia.

Results: The sensitivity of the CSP test for the entire studied population (n = 2484) was 94.

Involvement of the intrinsic and extrinsic cell-death pathways in the induction of apoptosis of mature lymphocytes by the Escherichia coli heat-labile enterotoxin.

Escherichia coli heat-labile enterotoxin (LT) exhibits a broad range of immunomodulatory activities, including the induction of lymphocyte-programmed cell death. In previous studies, we have demonstrated that in vivo LT promotes apoptosis of immature T and B cells through the stimulation of endogenous glucocorticoids. In the present study, we show that the extrinsic cell-death pathway as well as the apoptosis-inducing factor do not participate in the LT-induced elimination of thymocytes.

Epidemiological evaluation of Chagas disease in a rural area of southern Bolivia.

We evaluated the prevalence of Chagas disease using a rapid screening test (Chagas Stat-Pak), confirmed by ELISA, in Caraparí, a village of 9000 inhabitants in southern Bolivian Chaco. The prevalence of Trypanosoma cruzi was estimated in a sample of 995 people. The prevalence adjusted on age was 51.

Th17 development and autoimmune arthritis in the absence of reactive oxygen species.

Dendritic cells (DC) express a functional NADPH oxidase and produce reactive oxygen species (ROS) upon interaction with microbes and T cells. Exposure to ROS leads to DC activation and maturation, as evidenced by phenotypic and functional changes. We have evaluated how endogenous ROS production affects the cytokine secretion pattern and T cell-activating capacity of bone marrow-derived murine DC.