Gut Helicobacter presentation by multiple dendritic cell subsets enables context-specific regulatory T cell generation

Generation of tolerogenic peripheral regulatory T (pTreg) cells is commonly thought to involve CD10

ZBTB32 restrains antibody responses to murine cytomegalovirus infections, but not other repetitive challenges

ZBTB32 is a transcription factor that is highly expressed by a subset of memory B cells and restrains the magnitude and duration of recall responses against hapten-protein conjugates. To define physiological contexts in which ZBTB32 acts, we assessed responses by Zbtb32-/- mice or bone marrow chimeras against a panel of chronic and acute challenges. Mixed bone marrow chimeras were established in which all B cells were derived from either Zbtb32-/- mice or control littermates. Chronic infection of Zbtb32-/- chimeras with murine cytomegalovirus led to nearly 20-fold higher antigen-specific IgG2b levels relative to controls by week 9 post-infection, despite similar viral loads. In contrast, IgA responses and specificities in the intestine, where memory B cells are repeatedly stimulated by commensal bacteria, were similar between Zbtb32-/- mice and control littermates. Finally, an infection and heterologous booster vaccination model revealed no role for ZBTB32 in restraining primary or recall antibody responses against influenza viruses. Thus, ZBTB32 does not limit recall responses to a number of physiological acute challenges, but does restrict antibody levels during chronic viral infections that periodically engage memory B cells. This restriction might selectively prevent recall responses against chronic infections from progressively overwhelming other antibody specificities.National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01AI99109, R01AI131680, U01AI131349, K08AI04991]; New York Stem Cell FoundationOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Targeting of B and T lymphocyte associated (BTLA) prevents graft-versus-host disease without global immunosuppression

One-time treatment with an antibody against BTLA provides long-term protection against graft-versus-host disease without affecting effector T cell responses to tumors or pathogens

C-reactive protein concentration as a significant correlate for metabolic syndrome: a Chinese population-based study. Endocrine 43

Abstract Increasing evidence suggests that chronic, lowgrade inflammation may be a common soil involving the pathogenesis of metabolic syndrome (MetS) and cardiovascular disease. We examined the association between C-reactive protein (CRP) concentration, an extensively studied biomarker of low-grade inflammation, and the MetS in a representative sample of Chinese adults in Taiwan. We performed a cross-sectional analysis of data from 4234 subjects [mean (±SD) age, 47.1 (±18.2) years; 46.4 % males] who participated in a population-based survey on prevalences of hypertension, hyperglycemia, and hyperlipidemia in Taiwan. CRP levels were measured by the immunoturbidimetric CRP-latex high-sensitivity assay. The MetS was defined by an unified criteria set by several major organizations. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated with logistic regression model. Overall, there were 938 subjects with MetS among 4,234 participants, resulting in a prevalence rate of 22.1 %. A significantly progressive increase in the prevalence of MetS across quartiles of CRP was observed (p for trend \0.001). Participants in the second, third, and upper quartiles of CRP had significantly higher risk of having MetS when compared with those in the lowest quartile [adjusted ORs (95 % CIs) were 2.18 (1.62-2.94), 4.39 (3.31-5.81), and 7.11 (5.39-9.38), respectively; p for trend \0.001]. Furthermore, there was a strong stepwise increase in CRP levels as the number of components of the MetS increased. The prevalence of MetS showed a graded increase according to CRP concentrations. The possible utility of CRP concentration as a marker for MetS risk awaits further evaluation in prospective studies

Pilot Scale Production of Highly Efficacious and Stable Enterovirus 71 Vaccine Candidates

BACKGROUND: Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. PRINCIPAL FINDING: In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and non-human primates. CONCLUSION: These results provide valuable information supporting the current cell-based serum-free EV71 vaccine candidate going into human Phase I clinical trials

Central CD4+ T cell tolerance: deletion versus regulatory T cell differentiation

The diversion of MHC class II-restricted thymocytes into the regulatory T (Treg) cell lineage, similarly to clonal deletion, is driven by intrathymic encounter of agonist self-antigens. Somewhat paradoxically, it thus seems that the expression of an autoreactive T cell receptor is a shared characteristic of T cells that are subject to clonal deletion and those that are diverted into the Treg cell lineage. Here, we discuss how thymocyte-intrinsic and -extrinsic determinants may specify the choice between these two fundamentally different T cell fates

Real-Time Epidemic Monitoring and Forecasting of H1N1-2009 Using Influenza-Like Illness from General Practice and Family Doctor Clinics in Singapore

10.1371/journal.pone.0010036PLoS ONE54