Foxp3+ T cells induce Perforin-Dependent Dendritic Cell Death in Tumor-Draining Lymph Nodes.

Regulatory T (Treg) cells limit the onset of effective antitumor immunity, through yet-ill-defined mechanisms. We showed the rejection of established ovalbumin (OVA)-expressing MCA101 tumors required both the adoptive transfer of OVA-specific CD8(+) T cell receptor transgenic T cells (OTI) and the neutralization of Foxp3(+) T cells. In tumor-draining lymph nodes, Foxp3(+) T cell neutralization induced a marked arrest in the migration of OTI T cells, increased numbers of dendritic cells (DCs), and enhanced OTI T cell priming. Using an in vitro cytotoxic assay and two-photon live microscopy after adoptive transfer of DCs, we demonstrated that Foxp3(+) T cells induced the death of DCs in tumor-draining lymph nodes, but not in the absence of tumor. DC death correlated with Foxp3(+) T cell-DC contacts, and it was tumor-antigen and perforin dependent. We conclude that Foxp3(+) T cell-dependent DC death in tumor-draining lymph nodes limits the onset of CD8(+) T cell responses.

CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells.

Recent studies have challenged the view that Langerhans cells (LCs) constitute the exclusive antigen-presenting cells of the skin and suggest that the dermal dendritic cell (DDC) network is exceedingly complex. Using knockin mice to track and ablate DCs expressing langerin (CD207), we discovered that the dermis contains five distinct DC subsets and identified their migratory counterparts in draining lymph nodes. Based on this refined classification, we demonstrated that the quantitatively minor CD207+ CD103+ DDC subset is endowed with the unique capability of cross-presenting antigens expressed by keratinocytes irrespective of the presence of LCs. We further showed that Y-Ae, an antibody that is widely used to monitor the formation of complexes involving I-Ab molecules and a peptide derived from the I-E alpha chain, recognizes mature skin DCs that express I-Ab molecules in the absence of I-E alpha. Knowledge of this extra reactivity is important because it could be, and already has been, mistakenly interpreted to support the view that antigen transfer can occur between LCs and DDCs. Collectively, these data revisit the transfer of antigen that occurs between keratinocytes and the five distinguishable skin DC subsets and stress the high degree of functional specialization that exists among them.

The deep-sea chiton Nierstraszella (Mollusca: Polyplacophora: Lepidopleurida) in the Indo-West Pacific: taxonomy, morphology and a bizarre ectosymbiont

This study investigated the taxonomy and distribution of the deep-sea polyplacophoran mollusc Nierstraszella Sirenko, 1992 in the Indo-West Pacific, based on a collection of 516 specimens collected in the Philippines and Solomon Islands. Although seven species names have historically been proposed in this group of chitons, all have been considered as synonyms of the monotypic N. lineata (Nierstrasz, 1905). Morphological examination of this new material reveals the presence of two species. N. lineata is distinct from N. andamanica (Smith, 1906), based on morphological characters given in the original species description and very distinctly different morphology of aesthete pores in the shell surface. Furthermore, populations of N. andamanica in the Philippines and Solomon Islands are locally colonized with the epibiotic (ectoparasitic) bryozoan Pseudobathyalozoon profundum d'Hondt, 2006. These bryozoans attach ventrally to the girdle of the host chiton and the erect zooids feed within the pallial cavity, among the chiton's gills.

The Role of Direct Presentation by Donor Dendritic Cells in Rejection of Minor Histocompatibility Antigen-Mismatched Skin and Hematopoietic Cell Grafts

Background. The success of transplantation is hampered by rejection of the graft by alloreactive T cells. Donor dendritic cells (DC) have been shown to be required for direct priming of immune responses to antigens from major histocompatibility complex-mismatched grafts. However, for immune responses to major histocompatibility complex-matched, minor histocompatibility (H) antigen mismatched grafts, the magnitude of the T-cell response to directly presented antigens is reduced, and the indirect pathway is more important. Therefore, we aimed to investigate the requirement for donor DC to directly present antigen from minor H antigen mismatched skin and hematopoietic grafts.

Effect of the incorporation of hydroxy-terminated liquid silicones on the cure characteristics, morphology, and release of a model protein from silicone elastomer-covered rods

Silicone elastomer systems have previously been shown to offer potential for the sustained release of protein therapeutics. However, the general requirement for the incorporation of large amounts of release enhancing solid excipients to achieve therapeutically effective release rates from these otherwise hydrophobic polymer systems can detrimentally affect the viscosity of the precure silicone elastomer mixture and its curing characteristics. The increase in viscosity necessitates the use of higher operating pressures in manufacture, resulting in higher shear stresses that are often detrimental to the structural integrity of the incorporated protein. The addition of liquid silicones increases the initial tan delta value and the tan delta values in the early stages of curing by increasing the liquid character (G '') of the silicone elastomer system and reducing its elastic character (G'), thereby reducing the shear stress placed on the formulation during manufacture and minimizing the potential for protein degradation. However, SEM analysis has demonstrated that if the liquid character of the silicone elastomer is too high, the formulation will be unable to fill the mold during manufacture. This study demonstrates that incorporation of liquid hydroxy-terminated polydimethylsiloxanes into addition-cure silicone elastomer-covered rod formulations can both effectively lower the viscosity of the precured silicone elastomer and enhance the release rate of the model therapeutic protein bovine serum albumin. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

SEM-EDX of morphology of electroless nickel coatings with tin and tungsten

Electroless plating of binary Ni-P, ternary Ni-Sn-P and Ni-W-P, and quaternary Ni-W-Sn-P alloy coatings was carried out in alkalicitrate baths. After the plating, several kinds of test were carried out to determine the improvement in the characteristics and properties due to the additional elements as well as to study the change in behaviour when heat treatment was applied to these coatings. The coatings were subjected to X-ray diffraction analysis where it was found that all the coatings were amorphous. Interesting surface morphology features were examined using scanning electron microscopy. Addition of a third element improved the hardness.

Morphology, barrier, and mechanical properties of biaxially deformed poly(ethylene terephthalate)-mica nanocomposites

Nanocomposites of poly(ethylene terephthalate) PET with a partially synthetic fluoromica were prepared by melt mixing and extruded into sheet and subjected to large-scale biaxial stretching. Transmission electron microscopy (TEM) analysis of the mica tactoids showed that biaxial stretching had caused the tactoids to be more orientated and with improved exfoliation. The moduli of the nanocomposites were enhanced with increasing mica loading and the reinforcement effect was higher when the stretch ratio was 2 or 2.5, accommodated by having more aligned tactoids and reduced agglomeration. Enhancement in modulus was less pronounced for a stretch ratio of 3. Storage modulus was enhanced more significantly above the glass transition temperature. The barrier properties were enhanced by addition of mica before and after stretching. The Halpin-Tsai theory underpredicted the relative modulus of the PET nanocomposites, whereas the Nielsen model over-predicted the relative permeability. POLYM. ENG. SCI., 2012. (c) 2011 Society of Plastics Engineers

Langerin(+) Dermal Dendritic Cells Are Critical for CD8(+) T Cell Activation and IgH gamma-1 Class Switching in Response to Gene Gun Vaccines

The C-type lectin langerin/CD207 was originally discovered as a specific marker for epidermal Langerhans cells (LC). Recently, additional and distinct subsets of langerin(+) dendritic cells (DC) have been identified in lymph nodes and peripheral tissues of mice. Although the role of LC for immune activation or modulation is now being discussed controversially, other langerin(+) DC appear crucial for protective immunity in a growing set of infection and vaccination models. In knock-in mice that express the human diphtheria toxin receptor under control of the langerin promoter, injection of diphtheria toxin ablates LC for several weeks whereas other langerin(+) DC subsets are replenished within just a few days. Thus, by careful timing of diphtheria toxin injections selective states of deficiency in either LC only or all langerin(+) cells can be established. Taking advantage of this system, we found that, unlike selective LC deficiency, ablation of all langerin(+) DC abrogated the activation of IFN-gamma producing and cytolytic CD8(+) T cells after gene gun vaccination. Moreover, we identified migratory langerin(+) dermal DC as the subset that directly activated CD8(+) T cells in lymph nodes. Langerin(+) DC were also critical for IgG1 but not IgG2a Ab induction, suggesting differential polarization of CD4(+) T helper cells by langerin(+) or langerin-negative DC, respectively. In contrast, protein vaccines administered with various adjuvants induced IgG1 independently of langerin(+) DC. Taken together, these findings reflect a highly specialized division of labor between different DC subsets both with respect to Ag encounter as well as downstream processes of immune activation. The Journal of Immunology, 2011, 186: 1377-1383.