“
“Maternal Adriamycin molecular weight immune responses during pregnancy are critical in programming the future health of a newborn. The maternal immune system is required to accommodate fetal immune tolerance as well as to provide a protective defence against infections for the immunocompromised mother and her baby during gestation and lactation. Natural immunity and antibody production by maternal B

cells play a significant role in providing such immunoprotection. However, aberrations in the B cell compartment as a consequence of maternal autoimmunity can pose serious risks to both the mother and her baby. Despite their potential implication in shaping pregnancy outcomes, the role of B cells in human pregnancy

has been poorly studied. This review focuses on the role of B cells and the implications of B cell depletion therapy in pregnancy. It highlights the evidence of an association between aberrant B cell compartment and obstetric conditions. It also alludes to the potential mechanisms that amplify these B cell aberrances and thereby contribute to exacerbation of some maternal autoimmune conditions and poor neonatal outcomes. Clinical and experimental evidence suggests strongly that maternal autoantibodies contribute directly to the pathologies of obstetric and neonatal conditions that have significant implications for the lifelong health of a newborn. The evidence for clinical benefit and safety of B cell depletion therapies in pregnancy is reviewed, and an argument MI-503 manufacturer is mounted for further clinical evaluation of B cell-targeted therapies in high-risk pregnancy, with an emphasis on improving neonatal outcomes and prevention of neonatal conditions such as congenital heart block and fetal/neonatal alloimmune thrombocytopenia. An individual’s lifetime

health is critically programmed during the gestational period. During pregnancy, the maternal immune system is required not only to accommodate the allogeneic fetus but also to maintain protection against Ribonuclease T1 harmful infections in the otherwise immunocompromised mother and immuno-incompetent fetus [1]. The roles of innate and cell-mediated immunity, including natural killer, T helper type 1 or 2 (Th1/Th2) cells and regulatory T cells (Treg) are well documented in pregnancy [2, 3]. In contrast, there has been little focus on the role of B cells and antibody-mediated immunity. This is surprising, given the fundamental role of B cells as effectors and regulators of both innate and adaptive immune responses [4, 5]. Maternal B cells also provide a vital source of antibody-mediated protective immunity for the mother and her baby during both pregnancy and lactation [6].

Each data was analyzed by multivariate analysis. Results: Serum levels of IgA, Gd-IgA1, Gd-IgA1-specific IgG and Gd-IgA1-specific IgA were elevated in patients with IgAN compared with disease controls and healthy controls. However, none of the biomarkers alone fully differentiated IgAN patients from disease controls. Therefore, we re-analyzed these biomarkers and compared them with clinical data, such as age, gender, serum creatinine, urinary protein/creatinine ratio and degree of microscopic hematuria by combination. In accordance of analysis, we omitted

unnecessary variables from analysis using Principal Component Analysis (PCA) that is a variable reduction procedure to analyze the importance of each variable. Then, each GSK2118436 cell line variable were analyzed using logistic model. This model differentiated IgAN patients from disease controls with 81% specificity and 91% sensitivity. Conclusion: Our results suggest that serum Gd-IgA1 and Gd-IgA1-specific antibodies (IgG and IgA) are useful biomarkers for diagnosis of IgAN. The novel quantitative scoring system can be applied for diagnosis of IgAN besides renal biopsy. SUZUKI HITOSHI1, YANAGAWA HIROYUKI1, SUZUKI YUSUKE1, SATAKE KENJI1, JULIAN BRUCE A2,3, NOVAK JAN3, TOMINO YASUHIKO1 1Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine; 2Department of Medicine, University of Alabama at Birmingham;

3Department of Microbiology, University of Alabama at Birmingham Introduction: IgA nephropathy (IgAN) is an autoimmune Palbociclib molecular weight glomerulonephritis that immune complexes (IC) composed of galactose-deficient IgA1 (Gd-IgA1) and

anti-glycan IgG autoantibodies deposit in the glomeruli. Serum levels of Gd-IgA1 as well as anti-glycan IgG autoantibodies, responsible for the ADAMTS5 formation of ICs with Gd-IgA1, are elevated in patients with IgAN. However, the pathogenic roles of Gd-IgA1-containing IC and mechanisms of immune deposits in the mesangium are still obscure. Methods: Polymeric Gd-IgA1 myeloma protein and recombinant anti-glycan IgG were used to form IC (Gd-IgA1-IgG IC) in vitro to inject i.v. into nude mice. After various time intervals, mice were sacrificed; blood and urine were collected to determine serum IgA1 and IgG, urinary protein and creatinine and hematuria. Furthermore, to assess the potential capacity of these IC to activate endothelial cells, human renal glomerular endothelial cells (HRGEC) were co-cultured with Gd-IgA1 alone or Gd-IgA1-IgG IC for 72 h. Then, transcript levels of TNF-a, TGF-b, IL-6, ICAM1 and E-selectin in HRGEC were measured by RealTime PCR. Results: Gd-IgA1 and anti-glycan IgG formed IC that deposited with murine C3 in the mesangium and in small amounts in the subendothelial area of the glomerular capillaries, and induced hematuria and proteinuria. In control mice injected with only Gd-IgA1 or Gd-IgA1 with IgG from a healthy control, IgA1 deposited only transiently and did not cause tissue injury.

The

duration of surgery was 195 (163–275) minutes in group TIVA and 247 (174–276) in MK-8669 cell line group INHALATION. Blood samples were collected in tubes coated with ethylenediaminetetraacetic acid (EDTA), 7.2 mg EDTA per 4.5 ml blood. After centrifugation for removal of cells, the samples were frozen within 30 min and stored at −80 °C. The blood samples provided data on the levels of complement split products (C3a and SC5b-9), pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8) and anti-inflammatory cytokines (IL-4 and IL-10). The levels of TNF-α, IL-1β, IL-4, IL-6, IL-8 and IL-10 were obtained with SearchLight method (Pierce Biotechnology, Woburn, MA, USA), which is a multiplex sandwich enzyme-linked immunosorbent assay (ELISA) in a planar, plate-based array format,

for the quantitative measurement of secreted proteins in different biological materials. Diluted samples and controls were incubated for one hour on the arrayed plates. All incubations were performed at room temperature SB203580 chemical structure with shaking at 200 rpm. The plates were decanted and washed six times before adding a cocktail of biotinylated detection antibodies to each well. After incubating with detection antibodies for 30 min, the plates were washed three times and incubated for 30 min with streptavidin–horseradish peroxidase. The plates were again washed before adding SuperSignal Femto Chemiluminescent substrate. The plates were immediately imaged using the SearchLight Black Ice imaging system, and data were analysed using Array Analyst software (Auchon Clomifene Biosystems, Billerica, MA, USA). All results were in the range of the standard curve. Differences in age, duration of anaesthesia and surgery, blood loss, American Society of Anesthesiologists (ASA) physical status classification scores and length of stay at hospital post-operatively were tested between the treatment groups using Mann–Whitney U-tests. Chi-squared tests were used to compare proportions. Mean values of each inflammatory marker for each anaesthetic treatment group at each measurement point were inspected graphically. The repeated measurements were

then analysed using linear mixed models with an unstructured covariance structure and maximum likelihood estimates for both all patients and those without inflammatory bowel disease (IBD). All exploratory and formal statistical tests were carried out using SPSS for Windows (Version 18; SPSS Inc, Chicago, IL, USA). All P-values were two-tailed, and P-values <0.05 were considered statistically significant. There were no significant differences between the anaesthesia groups regarding clinical parameters. The parameters are given in Table 1. Complement and interleukin determinations are given in Table 2 and in Figs. 1–6. The C3a levels were increased during surgery in both groups compared with baseline (P < 0.001).

This highlights the role of C5a, the inflammatory pathway rather than the lytic terminal pathway. The observation that the terminal complement pathway, i.e., effector functions downstream of the C5 level, is of minor relevance for the cytokine response to buy Tanespimycin Candida infection is in agreement with the fact that this fungus has cell walls that are resistant to TCC insertion [[13]]. So far,

the C3 effector function—especially for opsonization—was considered important for the host response to Candida infections. The study by Cheng et al. [[1]] now defines the important role of the C5a activation peptide for the cellular inflammatory response to Candida. The inflammatory response mediated by complement was and still is underestimated. C5a reacts with two human receptors, C5aR and C5L2, and can induce a “cytokine storm” resulting in the systemic inflammatory disease sepsis, and this can lead to multi-organ failure [[18, 19]]. Currently, the role of C5a and the two human C5a receptors is an important topic of inflammatory research, and options for therapeutic intervention, such as in sepsis, are under intense discussion and development. The C5a-mediated inflammatory response is also highly relevant in autoimmune diseases, and the inhibition of this pathway is currently being investigated for therapeutic purposes. The C5-targeting humanized antibody Eculizumab is licensed for the treatment of complement-mediated disease,

such as PNH (paroxysmal

nocturnal hemoglobinuria) and aHUS (atypical hemolytic uremic syndrome) [[20]]. Eculizumab blocks C5, and neither inflammatory C5a nor TCC is generated. However, patients selleck chemicals llc treated with Eculizumab need to be vaccinated against Neisseria meningitides; therefore the question arises whether, similar to immunosuppressed HIV patients, individuals treated with Eculizumab as well as other complement buy Gemcitabine inhibitors are at an increased risk for fungal infections. Nevertheless, several PNH patients who have used this drug for several years show no severe side effects and no increased rate of fungal or other infections thus far [[21]]. The activated complement cascade forms a powerful line of defense against invading microbes. However, given that both C. albicans and A. fumigatus survive in a complement-competent host, these two related fungal pathogens apparently efficiently control and evade host complement attack. Cheng et al. [[14]] also address this issue from the pathogen angle by analyzing whether and how the pathogenic fungus responds and modulates the inflammatory complement challenge. The authors use genetically modified Candida that has a deleted Pra1 gene. Pra1, which was initially identified as a gene induced upon pH challenge, is a multipurpose complement and immune inhibitor [[16, 22]]. Pra1 is expressed on the fungal surface, is secreted into the surrounding medium and, once secreted, Pra1also binds back to the surface of both Candida yeast cells and hyphae.

enterica Enteritidis African invasive isolate D24954 and laboratory strain PT4. The differential kinetics between cell-free killing and phagocytosis of invasive nontyphoidal Salmonella allows these bacteria to escape

the blood and establish intracellular infection before they are killed by the membrane attack complex. “
“Th1 cell-mediated adaptive immune response is very important but may not be sufficient to control Mycobacterium tuberculosis (M. tuberculosis) infection. The roles RG7204 datasheet of the various T cell subsets and cytokines in the inflammatory processes are not clearly elucidated. We investigated whether Th1, Th22 and Th17 cells mediated cellular immunity at the local site of M. tuberculosis infection in patients with tuberculous pleurisy (TBP).

The results showed that the cytokines IFN-γ and IL-22 but not IL-17 were elevated in tubercular pleural fluid. Following stimulation with immune-dominant peptides of early secreted antigenic target-6 (ESAT-6), culture filtrate protein-10 (CFP-10) or Bacille Calmette–Guerin, pleural fluid mononuclear cells expressed high levels of cytokines IFN-γ, IL-22 and IL-17 as revealed by mRNA and protein measurements. In addition, we showed that cytokines IFN-γ, IL-22 and IL-17 were produced in M. tuberculosis-specific immune response by distinct subsets of CD4+ T cells with the phenotype of CD45RA−CD62L−CCR7+CD27+. Our results demonstrated for the first time that ESAT-6- and CFP-10-specific Th1, Th22 and Th17 BI 6727 nmr cells existed in the patients with TBP and might

play an essential role against M. tuberculosis infection. The findings of this study raised the possibility of unravelling the critical targets for therapeutic intervention in chronic inflammatory diseases such as TBP. Tuberculosis (TB) is considered Galactosylceramidase to be a global emergency. Approximately nine million people worldwide develop TB and 1.6 million people die of TB each year [1]. The vaccine administered to infants for TB is Bacille Calmette–Guerin (BCG), which has only limited efficacies. BCG protects against disseminated forms of TB in children, but it fails to protect against highly prevalent pulmonary tuberculosis (PTB) infection in adults [2, 3]. Importantly, it has been reported that approximately 90% of Mycobacterium tuberculosis-infected people develop a latent infection with no apparent clinical consequences. TB develops in approximately 10% of M. tuberculosis-infected individuals [3]. Therefore, there is an urgent need to understand the mechanisms of immune defence to help to control the epidemic. The Th1 cell-mediated adaptive immune response to M. tuberculosis infection is very important but not enough to control the disease [4–7]. However, the roles of the various T cell subsets and cytokines in the inflammatory processes are not clearly elucidated. In addition to IFN-γ, both IL-22 and IL-17 may contribute to the local immune response against M. tuberculosis infection.

Each unique parameterization of the model specifies one ‘virtual NOD mouse’, and each virtual mouse is validated by extensive comparisons of simulated responses against published data (see below). This approach focuses on finding BVD-523 biologically feasible parameterizations that reproduce critical behaviours, rather than on exact characterization of numerous difficult-to-measure parameters. In support

of our approach focusing on behavioural validation and prediction, a recent analysis of 17 other systems biology models, some with more than 200 parameters, suggests that attention to predictive accuracy, rather than parametric precision, is critical and can provide scientific value in areas where biological relationships are characterized incompletely [3]. Other models of type 1 diabetes have provided valuable insight into disease pathogenesis or health care optimization (e.g. [4–9]). As this model was designed to support drug development, it differs from existing models in the following areas. First, our model includes multiple contributors to the pathogenic process in order to support physiologically based representation of a diverse

https://www.selleckchem.com/products/bay-57-1293.html set of therapeutic strategies. Second, we model multiple disease stages, tracking autoimmune pathogenesis from initiation through diabetes onset in order to investigate relative efficacy associated with interventions applied at different disease stages. It should be noted that the focus of our model (and most corresponding NOD mouse research) is on disease prevention or remission, not disease management. Finally, our model represents the physiologically based interactions leading to destruction of β cells, differentiating it from Archimedes, another large-scale diabetes model which (-)-p-Bromotetramisole Oxalate includes detailed representation of metabolic responses, health care and complications, but in which disease results from a mathematical combination of epidemiological factors [8]. This paper is a biology-focused description of the Type 1 Diabetes PhysioLab platform intended

to introduce the model at a level of detail appropriate for understanding its research applications. Due to its size, a full mathematical description of the entire platform is not reasonable within the body of text. However, to illustrate our modelling approach, the equations, assumptions and data sources for a key module, islet CD8+ T lymphocytes, are summarized in Appendix S1, along with textual explanations. Further, the full model is available freely online as a downloadable file, including all equations, parameters, references, documentation, simulated intervention experiments reproducing published protocols and their associated simulation results (Appendix S2). We applied a top-down, outcomes-focused approach in developing the Type 1 Diabetes PhysioLab platform.

The mixed peritoneal cells were sedimented by centrifugation at 400×g for 5 min and resuspended in 8 mL of 70% isotonic Percoll solution (GE Healthcare, England). DMEM (2 mL) was laid on the top and the cells were centrifuged at 580×g for 15 min. MCs were recovered at the bottom of the gradient, washed and cultured overnight in complete DMEM supplemented with IL-3 (20 ng/mL). Purification was confirmed by toluidine

blue staining and by flow cytometry with anti c-kit and anti FcεRI antibodies (eBiosciences). Purity was usually more than 98%. The human LAD2 MC line was kindly provided by A. Kirshenbaum (NIH, Bethesda, MD, USA). The cell line was established from bone marrow aspirates of patient with MC sarcoma leukemia and is closely related to human MCs 35. LAD2 cells were grown in serum-free medium StemPro-34 (Invitrogen, Carlsbad, CA, USA) containing 2 mM glutamine INK 128 purchase and 100 ng/mL human stem-cell factor (Peprotech) and were periodically tested for c-Kit and FcεRI expression on the cell surface by flow cytometry (FACScan, Becton Dickinson). Human CD3+CD4+ T cells were selected from peripheral blood mononuclear cells by immunomagnetic cell sorting (Miltenyi Copanlisib in vivo Biotech). The CD4+CD25high cells were then purified from the CD3+CD4+ T cell fraction by FACSAria sorter (Becton Dickinson). Before experiments, 1×106/mL murine MCs (BMMCs and PMCs) were sensitized in medium without IL-3 for 4 h with 1 μg/mL

of DNP-specific IgE and washed twice with Tyrode’s buffer (10 mM HEPES buffer (pH 7.4), 130 mM NaCl, 5 mM KCl, 1.4 mM CaCl2, 1 mM MgCl2, 5.6 mM glucose and 0.1% BSA). Equal number

of murine MCs and CD4+CD25+ Tregs (ratio 1:1) were challenged with DNP-HSA (Sigma-Aldrich) in Tyrode’s buffer/0.05% BSA. LAD2 cells were overnight presensitized with 1 μg/mL of human myeloma IgE (Chemicon, Millipore, USA) and challenged in Tyrode’s buffer/0.05% BSA with 2 μg/mL of anti-human IgE (Sigma-Aldrich) in the presence or absence of equal number of human CD4+CD25+ T cells (ratio 1:1). The formation of MC–Treg conjugates in real time was analyzed by time-lapse epiluminescent microscopy using the Leica AF6000LX system (microscope, DMI6000 B; camera, DFC350FX; software: LAS AF). In 4��8C total, 0.5×106 pre-sensitized MCs and 0.5×106 Tregs (ratio 1:1) were plated on glass bottom Petri dishes (Nunc). The chamber was placed on heating plate pre-warmed at 37°C and DNP was added. Phase-contrast images were recorded at indicated time points and resulting video-recorded movies were processed with the Photoshop Cs3 software. At different time points (1, 5 and 20 min) the number of MCs in contact with Tregs was counted and the percentage of Treg-conjugated MCs over total MCs per field was calculated. Nearly 45±10 MCs were analyzed per condition at indicated time points. For each condition, video-recorded movies were performed in duplicate using different cell cultures (MC+Treg WT n=8 movies; MC+Treg OX40−/− n=6 movies).

3b-2, b-3) (17). We also found that clustering of RILP in the perinuclear regions was disrupted and diffused by the expression

of Rab7T22N. Collectively, our data demonstrate that Rab7 is vital for recruiting RILP to phagosomes during the maturation process, but not for recruiting CD63. How M.tb escapes the effects of the bactericidal components within the phagosome while still acquiring nutrients for growth is very important question. It has been suggested that mycobacterial phagosomes arrest their maturation at an early stage and completely avoid fusion with lysosomes (18, 19). However, we have shown the localization of CD63 (Fig. 2) and LAMP-2 (4) on M.tb phagosomes in macrophages. It Neratinib price has been proposed that phagolysosome biogenesis is achieved by a series of fusions with heterogeneous lysosomes (20). This model is supported by a report demonstrating the existence of sub-populations of lysosomes in macrophages (6). Our previous and current studies demonstrating the alternative localization of lysosomal markers on M.tb phagosomes further support this model. From these observations, it seems that dissociation

of Rab7 from M.tb phagosomes selectively inhibits fusion with harmful lysosomes despite continued fusion with non-microbicidal lysosomes. In conclusion, based on our findings we propose the following model for M.tb-induced inhibition of phagolysosome biogenesis: Early M.tb phagosomes are capable of recruiting Rab7 and can potentially fuse with lysosomes. RILP is also recruited to M.tb phagosomes, which form the Rab7-RILP-dynein/dynactin protein complex followed by promotion of Selleck Gefitinib phagolysosome biogenesis. However, viable M.tb is able to release Rab7 from phagosomes, resulting in inhibition of further fusion with lysosomal vesicles and disassembly of the RILP-phagosome complex. This causes the blocking of subsequent phagolysosome biogenesis. RANTES On the other hand, non-microbicidal vesicles expressing CD63 and/or LAMP-2 continuously fuse with M.tb phagosomes

despite Rab7 dissociation, and this fusion would support the acquisition of nutrients for mycobacterial proliferation within the phagosome. We thank Drs. Toshi Nagata and Masato Uchijima (Hamamatsu University School of Medicine, Hamamatsu, Japan) for their helpful discussion. M.tb strain H37Rv was kindly provided by Dr. Isamu Sugawara (Research Institute of Tuberculosis, Tokyo, Japan). This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, COE Research and Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Health and Labor Science Research Grants for Research into Emerging and Reemerging Infectious Diseases from the Ministry of Health, Labor and Welfare of Japan, and the United States-Japan Cooperative Medical Science Committee.

The authors are grateful to Prof. Kathleen Reilly for comments and critical reading. This study was supported by a grant from the National Natural Science Foundation of China (No. 30872788) and Beijing Municipal Science Technology

Commission (No. Z09050700940903). J.X., L.S. and H.Y. contributed equally to this LDK378 chemical structure study. “
“The objective of this study was to determine whether there was any association between the peripheral blood CD4+ CD25+ Foxp3+ regulatory T cells (Treg cells) and implantation success in patients undergoing in vitro fertilization (IVF) treatment. Prospective observational study of 101 randomly selected women who underwent IVF treatment for tubal factor from May 2011 to June 2011. The percentage of peripheral blood Treg cells and the expression levels of Foxp3

and CTLA4 mRNA in peripheral blood mononuclear cells (PBMCs) were recorded and their relations to IVF treatment outcomes were analyzed. Treg cells were significantly elevated in the pregnant group (P = 0.03). The expression level of Foxp3 mRNA in PBMCs from pregnant group also significantly increased (P = 0.02). A receiver operating characteristic analysis (area under curve = 0.631) found that those women with Treg cells >0.6%, the pregnancy rate and live birth rate were much higher as compared to women with Treg cells below this level (P < 0.05). An increase of Treg FK506 cells in the peripheral blood was associated with a

better IVF treatment outcome (OR 4.3, 95% CI = 1.76–10.48), with a sensitivity of 64%, specificity of 71%. An elevated level of circulating Treg cells was associated with increased rates of pregnancy and live birth in IVF treatment. “
“This unit details methods for the isolation, in vitro expansion, and functional characterization of human iNKT cells. The term iNKT derives from the fact that a large fraction of murine NKT cells recognize the MHC class I-like CD1d protein, are CD4+ or CD4-CD8- (double negative), and use an identical “invariant” TCRα chain, which is generated by precise Vα14 and Jα281 (now renamed Jα18) rearrangements with either no N-region diversity or subsequent trimming to nearly identical amino-acid sequence (hence, ‘iNKT’). Basic Protocol 1 and Alternate Protocol 1 use multi-color to FACS analysis to identify and quantitate rare iNKT cells from human samples. Basic Protocol 2 describes iNKT cell purification. Alternate Protocol 2 describes a method for high-speed FACS sorting of iNKT cells. Alternate Protocol 3 employs a cell sorting approach to isolate iNKT cell clones. A Support Protocol for secondary stimulation and rapid expansion of iNKT cells is also included. Basic Protocol 3 explains functional analysis of iNKT. Curr. Protoc. Immunol. 90:14.11.1-14.11.17. © 2010 by John Wiley & Sons, Inc. “
“IL-23 is absolutely crucial for the development of T-cell driven autoimmune disease in mice.

gondii by flow cytometry. The mRNA and protein expression levels of transforming growth factor-β (TGF-β) and interleukin-17A (IL-17A) were analyzed using real-time this website PCR and enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of forkhead box P3 (Foxp3), retinoic acid–related orphan receptor γt (RORγt), and IL-6 were also

analyzed using real-time PCR. The correlations of the ratio of Treg/Th17 to the mRNA or protein expression level of those factors were analyzed by Spearman’s correlation analysis. Data were analyzed by unpaired t-test and paired t-test. Results  The proportion of Tregs or Th17 cells in the placenta and spleens of the T. gondii-infected pregnant mice was significantly lower or higher than in those of non-infected mice, respectively. Upregulation of TGF-β and downregulation of IL-17A were found in the placenta of T. gondii-infected pregnant mice. The ratio of Treg to Th17 was significantly lower in the infected mice than that in the non-infected mice (P < 0.01).The ratio of Treg to Th17 positively or negatively correlated with the protein expression level of TGF-β (r = 0.6204,

P < 0.05) or IL-17A (r = −0.6296, P < 0.05), respectively. The ratio also positively correlated with the mRNA expression level of Foxp3 learn more (r = 0.7985, P < 0.01), but negatively correlated with the mRNA expression level of RORγt (r = −0.6153, many P < 0.05), and IL-6 (r = −0.7492, P < 0.01). Conclusion  TheTreg/Th17 imbalance exists in the pregnant mice infected with T. gondii, which is associated with the expression of related cytokine and key transcription factors. This result suggests that the embryo loss caused by this parasite may be associated with a reduced ratio of Treg to Th17 cell number. "
“Defective control of T cell apoptosis is considered to be one of the pathogenetic mechanisms in systemic lupus erythematosus (SLE). Oestrogen has

been known to predispose women to SLE and also to exacerbate activity of SLE; however, the role of oestrogen in the apoptosis of SLE T cells has not yet been documented. In this study, we investigated the direct effect of oestrogen on the activation-induced cell death of T cells in SLE patients. The results demonstrated that oestradiol decreased the apoptosis of SLE T cells stimulated with phorbol 12-myristate 13-acetate (PMA) plus ionomycin in a dose-dependent manner. In addition, oestradiol down-regulated the expression of Fas ligand (FasL) in activated SLE T cells at the both protein and mRNA levels. In contrast, testosterone increased FasL expression dose-dependently in SLE T cells stimulated with PMA plus ionomycin. The inhibitory effect of oestradiol on FasL expression was mediated through binding to its receptor, as co-treatment of tamoxifen, an oestrogen receptor inhibitor, completely nullified the oestradiol-induced decrease in FasL mRNA expression.