Search

Summary Dendritic cells (DCs) can induce both tolergenic as well as effective immune responses in the lung. Pulmonary DCs producing interleukin (IL)-10 mediated tolerance induced by respiratory exposure to antigen. IL-10 is an important immunosuppressive cytokine, which inhibits maturation and function of DC. To assess whether IL-10 producing DCs can exert the tolergenic effect through the differentiation of regulatory T cells, bone marrow derived DCs were genetically modified by IL-10 expressing adenovirus. IL-10 gene modified DCs (Ad-IL-10-DC) displayed a characteristic phenotype of immature DCs. Here we showed that in vitro repetitive stimulation of naïve DO11·10 CD4+ T cells with Ad-IL-10-DCs resulted in a development of IL-10 producing T-cell regulatory cells. These T cells could not proliferate well but also lost their ability to produce interferon-γ upon restimulation with irradiated splenocytes and ovalbumin peptide. Furthermore, in co-culture experiments these T cells inhibited the antigen-driven proliferation of naïve CD4+ T cells in a dose-dependent manner. Our findings demonstrated that IL-10 producing DCs had the potential to induce the differentiation of Tr1-like cells and suggested their therapeutic use.

The physical mechanism for ordering and the properties of lattice defects in {ital B}2-type transition-metal (TM) aluminides are presented. It is shown that the size effect is inadequate in explaining the defect structure (and ordering) in these intermetallics. Such is the case evident in the prototypical example of PdAl, which is found to exhibit all the physical characteristics of strongly ordered alloys even though the difference in atomic radii between constituent Pd and Al atoms is very small. We obtain a high heat of formation, high antiphase boundary energies associated with the partial 1/2{l_angle}111{r_angle} slip, and the existence of triple defect (for the point defect structure) in PdAl. Comparative analyses are presented for PdAl, NiAl, and FeAl, and results reveal that the electronic structure at the TM sites plays a decisive role in the energetics (and types) of defects. The strong ordering in late TM aluminides of the {ital B}2 type is due to the {ital lack} of electronic screening from the TM {ital d} band to compensate the energetically unfavorable nearest-neighbor interaction between Al atoms when ordering is disrupted.

We present a theory on the structural stability of aluminum-rich transition-metal (TM) compounds. Our approach incorporates electronic-structure-based potential-energy functions for the aluminides. It is shown that an argument based on the short-range Al-TM interactions can explain the transition from close-packed structures for early TM aluminides to open and complex structures for middle and late TM aluminides. On the other hand, the medium- and long-range interactions between the TM atoms are responsible for the particular choice of a close-packed (or complex) structure for a given aluminide.

Interleukin-1 (IL-1) is a proinflammatory cytokine and IL-1 receptor antagonist (IL-1ra) is a natural inhibitor that binds to IL-1 receptor type I without inducing signal transduction. It is suggested that IL-1 is required for allergen-specific T helper type 2 cell activation and the development of airway hyper-responsiveness (AHR), but the immunologic effect of exogenous IL-1ra in allergic asthma remains unclear. To examine the effect of IL-1ra on airway inflammation and immunoeffector cells in allergic asthma, recombinant adenovirus expressing human IL-1ra (Ad-hIL-1ra) was delivered intranasally into ovalbumin (OVA)-immunized mice. Single intranasal administration of Ad-hIL-1ra before airway antigen challenge in OVA-immunized mice significantly decreased the severity of AHR and reduced pulmonary infiltration of eosinophils and neutrophils. Suppression of IL-5 and eotaxin with concomitant enhancement of interferon gamma in bronchoalveolar lavage fluid was also noted in OVA-immunized mice by administration of Ad-hIL-1ra. In addition, histological studies showed that Ad-hIL-1ra was able to decrease OVA-induced peribronchial inflammation. Taken together, our results indicated that administration of Ad-hIL-1ra may have therapeutic potential for the immunomodulatory treatment of allergic asthma.

Allergic asthma is characterized by airway hyper-responsiveness (AHR) and cellular infiltration of the airway with predominantly eosinophils and Th2 cells. The normal resolution of inflammation in the lung occurs through the regulated removal of unneeded cells by Fas-Fas ligand-mediated apoptosis. Fas ligand (FasL) is a member of the tumor necrosis factor family, and when bound to Fas, it induces apoptosis of the cells. To examine the effect of the FasL gene on airway inflammation and immune effector cells in allergic asthma, recombinant adenovirus expressing murine FasL (Ad-FasL) was delivered intratracheally into ovalbumin (OVA)-immunized mice. We found that a single administration of Ad-FasL in OVA-immunized mice significantly alleviated AHR and eosinophilia by inducing the apoptosis of eosinophils and/or reducing eosinophil attractant factors, such as IL-5 and eotaxin levels. The number of infiltrated lymphocytes and Th2 cytokines, including IL-5 and IL-13, decreased in OVA-immunized mice by administration of Ad-FasL. KC and TNF-alpha production also decreased in Ad-FasL-treated OVA-immunized mice. These findings indicated that the administration of Ad-FasL to OVA-sensitized mice significantly suppressed pulmonary allergic responses. Although more studies are needed, these results suggested that Ad-FasL might be applied as an alternative therapy for allergic asthma.

The effect of external fields on the structural and electronic properties of Ag(110) is investigated using local-density-functional theory. We find that Ag(110) undergoes a (1×2) missing-row reconstruction as an excess charge of ≃0.05 electron per surface atom is added onto the surface. Our result supports an electron-donation mechanism for the alkali-metals-induced reconstruction on the (110) surface of the 3d and 4d fcc metals. The surface interlayer spacings are found to be insensitive to the applied field in the absence of field-induced surface reconstruction