Dynamical visualization of anisotropic electromagnetic re-emissions from a single metal micro-helix at THz frequencies.

The capability for actual measurements-not just simulations-of the dynamical behavior of THz electromagnetic waves, including interactions with prevalent 3D objects, has become increasingly important not only for developments of various THz devices, but also for reliable evaluation of electromagnetic compatibility. We have obtained real-time visualizations of the spatial evolution of THz electromagnetic waves interacting with a single metal micro-helix. After the micro-helix is stimulated by a broadband pico-second pulse of THz electromagnetic waves, two types of anisotropic re-emissions can occur following overall inductive current oscillations in the micro-helix. They propagate in orthogonally crossed directions with different THz frequency spectra. This unique radiative feature can be very useful for the development of a smart antenna with broadband multiplexing/demultiplexing ability and directional adaptivity. In this way, we have demonstrated that our advanced measurement techniques can lead to the development of novel functional THz devices.

Pretreatment of donor islets with the Na(+) /Ca(2+) exchanger inhibitor improves the efficiency of islet transplantation.

Pancreatic islet transplantation is an attractive therapy for the treatment of insulin-dependent diabetes mellitus. However, the low efficiency of this procedure necessitating sequential transplantations of islets with the use of 2-3 donors for a single recipient, mainly due to the early loss of transplanted islets, hampers its clinical application. Previously, we have shown in mice that a large amount of HMGB1 is released from islets soon after their transplantation and that this triggers innate immune rejection with activation of DC, NKT cells and neutrophils to produce IFN-γ, ultimately leading to the early loss of transplanted islets. Thus, HMGB1 release plays an initial pivotal role in this process; however, its mechanism remains unclear. Here we demonstrate that release of HMGB1 from transplanted islets is due to hypoxic damage resulting from Ca(2+) influx into ß cells through the Na(+) /Ca(2+) exchanger (NCX). Moreover, the hypoxia-induced ß cell damage was prevented by pretreatment with an NCX-specific inhibitor prior to transplantation, resulting in protection and long-term survival of transplanted mouse and human islets when grafted into mice. These findings suggest a novel strategy with potentially great impact to improve the efficiency of islet transplantation in clinical settings by targeting donor islets rather than recipients.

Involvement of MIP-2 and CXCR2 in neutrophil infiltration following injection of late apoptotic cells into the peritoneal cavity.

Apoptotic cells are cleared by phagocytes, such as macrophages, as soon as they appear in vivo. If apoptosis occurs acutely, however, macrophages may be outnumbered by apoptotic cells, which causes late apoptosis. We previously showed that injection of late apoptotic cells into the peritoneal cavity led to transient infiltration of neutrophils. In this study, we examined the involvement of MIP-2 and CXCR2 in the neutrophil infiltration. We first produced a recombinant MIP-2 protein, and a fusion protein between CXCR2 and GST in E. coli, and then generated anti-MIP-2 antibodies and anti-CXCR2 antibodies in rabbits. We then confirmed their specificity by Western blotting analysis and flow cytometry. Injection of late apoptotic cells, such as P388 cells treated with etoposide for 24 hours and CTLL-2 cells cultured in IL-2-free medium for 28 hours, induced neutrophil infiltration into the peritoneal cavity, as expected. The antibodies, but not control antibodies against GST, suppressed the neutrophil infiltration to the level caused by injection of normal (viable) cells, suggesting that MIP-2 and CXCR2 are mainly involved in the neutrophil infiltration caused by late apoptotic cells.

Skin antigens in the steady state are trafficked to regional lymph nodes by transforming growth factor-beta1-dependent cells.

Antigen capturing in the skin and antigen trafficking into regional lymph nodes (LN) initiate immune responses. In this study, employing melanin granule (MG) as an easily traceable antigen in two mouse strains that carried steel factor or hepatocyte growth factor transgenes and had melanocytosis in the epidermis or in the dermis respectively, we investigated the mechanism of antigen trafficking from the skin. MG captured in the epidermis or dermis accumulated in the regional LN, but not other tissues. Only in alymphoplastic mice did MG-laden cells pass through the lymphatics and reached many tissues. Since inflammatory regions were not observed in the skin of either type of transgenic mouse, our developmental system enables us to investigate constitutive capturing and trafficking of insoluble antigens in the steady state. Both dendritic cells and macrophages were laden with MG in the regional LN. To determine which cells traffic antigens to the LN, we prepared double mutants that carried the transgenes and lacked transforming growth factor (TGF)-beta1, since mice lacking TGF-beta1 are reported to be deficient of Langerhans cells. Few MG were observed in the regional LN of these double-mutant mice. We also showed that signaling via macrophage colony stimulating factor receptor or Flt3/Flk2 is not essential for development of the cells for this antigen trafficking. These results indicate that antigens in the epidermis and dermis in the steady state are trafficked into regional LN only by TGF-beta1-dependent cells, which may be a dendritic cell lineage.

The formation of immunogenic major histocompatibility complex class II-peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli.

During their final differentiation or maturation, dendritic cells (DCs) redistribute their major histocompatibility complex (MHC) class II products from intracellular compartments to the plasma membrane. Using cells arrested in the immature state, we now find that DCs also regulate the initial intracellular formation of immunogenic MHC class II-peptide complexes. Immature DCs internalize the protein antigen, hen egg lysozyme (HEL), into late endosomes and lysosomes rich in MHC class II molecules. There, despite extensive colocalization of HEL protein and MHC class II products, MHC class II-peptide complexes do not form unless the DCs are exposed to inflammatory mediators such as tumor necrosis factor alpha, CD40 ligand, or lipoplolysaccharide. The control of T cell receptor (TCR) ligand formation was observed using the C4H3 monoclonal antibody to detect MHC class II-HEL peptide complexes by flow cytometry and confocal microscopy, and with HEL-specific 3A9 transgenic T cells to detect downregulation of the TCR upon MHC-peptide encounter. Even the binding of preprocessed HEL peptide to MHC class II is blocked in immature DCs, including the formation of C4H3 epitope in MHC class II compartments, suggesting an arrest to antigen presentation at the peptide-loading step, rather than an enhanced degradation of MHC class II-peptide complexes at the cell surface, as described in previous work. Therefore, the capacity of late endosomes and lysosomes to produce MHC class II-peptide complexes can be strictly controlled during DC differentiation, helping to coordinate antigen acquisition and inflammatory stimuli with formation of TCR ligands. The increased ability of maturing DCs to load MHC class II molecules with antigenic cargo contributes to the >100-fold enhancement of the subsequent primary immune response observed when immature and mature DCs are compared as immune adjuvants in culture and in mice.

Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells.

Cells from the bone marrow can present peptides that are derived from tumors, transplants, and self-tissues. Here we describe how dendritic cells (DCs) process phagocytosed cell fragments onto major histocompatibility complex (MHC) class II products with unusual efficacy. This was monitored with the Y-Ae monoclonal antibody that is specific for complexes of I-Ab MHC class II presenting a peptide derived from I-Ealpha. When immature DCs from I-Ab mice were cultured for 5-20 h with activated I-E+ B blasts, either necrotic or apoptotic, the DCs produced the epitope recognized by the Y-Ae monoclonal antibody and stimulated T cells reactive with the same MHC-peptide complex. Antigen transfer was also observed with human cells, where human histocompatibility leukocyte antigen (HLA)-DRalpha includes the same peptide sequence as mouse I-Ealpha. Antigen transfer was preceded by uptake of B cell fragments into MHC class II-rich compartments. Quantitation of the amount of I-E protein in the B cell fragments revealed that phagocytosed I-E was 1-10 thousand times more efficient in generating MHC-peptide complexes than preprocessed I-E peptide. When we injected different I-E- bearing cells into C57BL/6 mice to look for a similar phenomenon in vivo, we found that short-lived migrating DCs could be processed by most of the recipient DCs in the lymph node. The consequence of antigen transfer from migratory DCs to lymph node DCs is not yet known, but we suggest that in the steady state, i.e., in the absence of stimuli for DC maturation, this transfer leads to peripheral tolerance of the T cell repertoire to self.

Photoinduced Magnetization of a Cobalt-Iron Cyanide

Photoinduced magnetization was observed in a Prussian blue analog, K0.2Co1.4- [Fe(CN)6]·6.9H2O. An increase in the critical temperature from 16 to 19 kelvin was observed as a result of red light illumination. Moreover, the magnetization in the ferrimagnetic region below 16 kelvin was substantially increased after illumination and could be restored almost to its original level by thermal treatment. These effects are thought to be caused by an internal photochemical redox reaction. Furthermore, blue light illumination could be used to partly remove the enhancement of the magnetization. Such control over magnetic properties by optical stimuli may have application in magneto-optical devices.