Natural Killer (NK) cells play important roles in host defense, especially the clearance of viral or bacterial infected cells and the elimination of tumor cells. NK cells have cytotoxicity against target cells as well as the ability of cytokine production. NK cells not only eliminate infected cells directly by cytotoxicicity but also induce acquired immunity by cytokines. These functions of NK cells are regulated by the balance of activating or inhibitory signaling. The inhibitory NK cell receptors are well understood, however, less is known about the activating signaling pathways. An activating receptor, NKG2D is expressed in all NK cells, γδ⁺T cells and activated/memory CD8⁺T cells. By recent studies, NKG2D is best characterized as an activating receptor. This review summarizes recent topics and our findings focus on the role of NKG2D in NK cells and in CD8⁺T cells, including tumor immunity and autoimmune diabetes.

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Despite the fact that intestinal IgA responses are known to be regulated by gut-associated lymphoreticular tissues (GALT), the exact sites where this regulatory network is formed are only partially understood. Our study shows that antigen-specific intestinal IgA antibodies are induced after oral immunization in mice made deficient in Peyer ’s patches (PP) by in utero treatment with lymphotoxin-β receptor and Ig (LTβR-Ig). These results suggest that the PP-independent pathways exist for antigen-specific intestinal IgA responses. On the other hand, postnatal LTβR-Ig-treated mice lacking isolated lymphoid follicles (ILF) were still able to produce significant mucosal IgA responses. Furthermore, mice treated with both TNF receptor p55 and Ig (TNFR55-Ig) and LTβR-Ig in utero, which lack PP and mesenteric lymph nodes (MLN) but retain intact ILF, failed to induce antigen-specific IgA responses after oral immunization. These findings demonstrated that ILF were not essential for induction of intestinal IgA responses. Interestingly, however, the IgA responses induced in the PP- or ILF- null mice were significantly lower than those seen in the control mice. Taken together, these findings suggest that aggregated lymphoid follicles residing in the intestinal lumen, e.g. PP and ILF, and draining MLN, may comprise an integrated regulatory network for the induction of maximum IgA antibody responses to orally administered antigens.

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Elimination of pathogenic bacteria harbored within host cells is crucial for host defense. Many pathogenic bacteria can enter professional or nonprofessional phagocytic cells to colonize, or disseminate to other cells. The endocytic degradation of pathway has been considered the only system against such intracellular pathogens. However, there is a second degradation system within the host cells, called autophagy. Autophagy is a physiologically important cellular process for the degradation of some organelles and cytosolic proteins within cells. Several studies have shown that some intracellularly invading bacteria are found within autophagosomes, however, it is still unclear whether these bacteria are vulnerable to autophagic destruction. Recently, we found that intracellularly invaded Streptococcus pyogenes (Group A Streptococcus; GAS) were selectively trapped by the autophagosome-like compartments and degraded upon fusion with lysosomes in non-phagocytic epithelial cells. In autophagosome formation-deficient Atg 5^-/- cells, such compartments were not formed upon GAS infection. These results indicate that the autophagic machinery is utilized not only for degradation of subcellular components, but also functions as an innate defense system against invading bacteria.

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Cytolethal distending toxin (Cdt) is a new bacterial toxin that hijacks the control systems of target cells. Cdt is composed of three subunits, CdtA, CdtB and CdtC, all of which form a tripartite complex, and are produced by several bacterial pathogens including Actinobacillus actinomycetemcomitans. CdtB is an active component, while CdtA and CdtC seem to carry CdtB into the cells. The sophisticated strategy of Cdt to control host cells is via CdtB-mediated limited DNA damage of the host cell chromosome, which triggers the response of the cell cycle checkpoint and results in G2 arrest in the cells. Cdt also induces apoptotic cell death of lymphocytes, which may damage host immunity. In vitro studies demonstrated that Cdt has potent cytotoxic activity to a variety of cells originated from periodontal tissues. Epidemiological studies indicated a high frequency of Cdt-positive A. actinomycetemcomitans in patients with periodontitis, suggesting its role in the onset and/or exacerbation of periodontitis.

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A general view of the origin and development of cementum is discussed. The evolutionary origin of the cementum is a lining bone tissue that ties the dermal bone to the dermal tooth in Ostradodermi (armored fish, Agnatha, cartilaginous vertebrate). The connective tissue around the dermal tooth forms it, and it is absorbed after connecting the tooth in tooth replacement. The odontoblast forming the dermal tooth loses its polarity, but the osteoblast which forms the lining bone remains multi-polar. Connective tissue forming the dermal tooth has further developed to form the pedicle and fibrous tissue connecting the teeth and jaw bones in fish and amphibians. In reptiles, teeth unite to the jaws with the pedicle bone, which is formed from the periodontal connective tissue. The formation aspect of the pedicle on the jaws differs from the dentine surface of the tooth root, because the pedicle is deposited on the jaw after absorption, but is directly deposited on the dentine. Some parts of the pedicle show as Sharpey’s fibers but others are similar to the hyaline cartilage structures. It has been shown that the formation mechanisms have two polarities, like the human periodontal membrane, between the jaws and tooth root.
Cementum is deposited not only on the surface of the root but also on the tooth crown as coronal cementum in mammals. When the coronal cementum develops, the enamel surface is absorbed by dental follicle tissue in horses etc., the enamel development is partially inhibited and forms a rugged surface in elephants etc., and enamel reduction is seen in Berardius (tooth whale). The ivory (lateral incisor) of the elephant and the tusk of the walrus (Odobenus) are covered in thick cementum; this is a root cellular cementum with rhythmic incremental lines, because the top of it has thin enamel.

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Human enamel tufts appeared as corrugated ribbon-like structures located on the dentin parallel to the tooth axis when observed under the binocular microscope and scanning electron microscope (SEM). SEM observation disclosed enamel tufts as bundles of well-extended tubular structures attributable to hypomineralized enamel sheaths. Plate-like structures, previously referred to as “tuft-root” ran in the center of the enamel tufts, connecting the dentin surface. When observing under the transmission electron microscope, the plates of tufts extended from the superficial layer of the dentin, penetrating the hypermineralized zone adjacent to the dentin-enamel (D-E) junction, and then, reaching the tuft region. In the tuft region, the plates of tufts ran mainly along the enamel sheaths and partially across the enamel prisms. The immuno-gold technique verified an intense immunoreactivity for amelogenin in the superficial layer of the dentin as well as the enamel prisms in the tufts, although no reaction was found over the “plates of tufts”. The immunoreactivity for 13-17 kd sheath proteins, also denoted as sheathlin, ameloblastin or amelin, was detected over the filamentous structures closely associated with the enamel sheaths in the enamel tuft. Thus, our study demonstrated that enamel tufts consist of both well extended hypomineralized enamel prisms and “plates of tufts”. The major organic substance of the enamel tufts is suggested to be 13-17 kd sheath proteins rather than amelogenin.

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The most potent antigen-presenting cells, dendritic cells (DCs), play an important role in the cellular antitumor response by taking up tumor antigens and stimulating the activity of antigen-specific T cells. The differentiation of DCs can be induced in bone marrow or peripheral blood cultures using cytokines such as granulocyte macrophage colony-stimulating factor, interleukin (IL)-4, and tumor necrosis factor-α. In recent years the application of DCs to immunotherapy has been challenged by various malignant neoplasms. It has been shown in cancer patients that cancer cells themselves produce and secrete immunosuppressive cytokines such as IL-10, transforming growth factor-β1, and vascular endothelial growth factor, which induce defective immune cell function and a defective host immune response. In this article we describe the suppression of DC differentiation and the possible application of DCs to immunotherapy in human squamous cell carcinoma of the oral cavity.

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Recently many new bacterial genera and species, such as genus Slackia, Eggerthella, Cryptobacterium and Mogibacterium, have been proposed on the basis of phylogenetic analysis and DNA-DNA similarity data. These organisms, isolated from periodontal pockets and other oral infectious lesions, are asaccharolytic anaerobic gram positive rods (AAGPR), and have been proven to be difficult to culture and unreactive in conventional biochemical tests. Molecular systematic techniques, including 16S rRNA gene sequencing analysis, have demonstrated that there is more diversity than previously thought in these AAGPR species. In addition, these sequences dates can be helpful for the construction of specific PCR primers for use in the rapid detection and identification of previously undescribed taxa. A complete description of the microbial flora associated with oral infections could lead to potential benefits in the elucidation of disease causation, and the development of novel diagnostic tools.

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In order to develop new treatments for oral candidiasis, Takakura, et al. recently established a new murine model of this condition showing local symptoms. The present article reviews studies using this murine model to ascertain the clinical application of essential oils, and antimicrobial agents found in saliva. Applying tea tree oil to the mouth of mice with C. albicans reduced the viable cell count and improved inflammatory symptoms. When mice were given tap water containing bovine lactoferrin, they were similarly also protected from oral candidiasis, but protection was clearly observed only from 6 days after infection. Furthermore, we were able to identify the existence of a factor which detached C. albicans that had attached to oral tissue by forming biofilms. When human saliva was administered to the mice orally inoculated with C. albicans, viable cell counts and inflammatory symptoms declined significantly. We expect this murine model of oral candidiasis to contribute to clarification of the host defense mechanisms against the disease, and to aid in the development of new therapeutic agents.

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The development of non-benzodiazepine drugs that have only the anxiolytic or sedative action of benzodiazepines started in the latter half of the 1980’s. These drugs have been developed using two approaches: development of partial benzodiazepine receptor agonists, and development of drugs with selectivity for the α subunit of the GABA_A receptor, at which the benzodiazepine receptor binding site exists. Anxioselective drugs have been developed using the former approach, whereas sedative-selective drugs have emerged from the latter.
The actions of the anxioselective drug Y-23684 and the sedative-selective drug zolpidem on the central nervous system have been studied by dual-probe microdialysis. This approach has shown that anxioselective drugs suppress accentuation of the locus coeruleus-medial prefrontal cortex norepinephrine neural activity under stress, while sedative-selective drugs suppress accentuation of the ventral tegmental area-nucleus accumbens dopamine neuron activity in the stress state. These findings suggest that the difference in the effect on the neural network relates to the selectivity for anxiolytic or sedative action.

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The genetics of tooth root length have not been extensively studied. This study was conducted to identify the quantitative trait loci (QTLs) involved in the determination of root length in mice. Mesial, palatal and distal root length (MR, PR, and DR, respectively) of the upper first molar (M¹) and DR of the lower first molar (M₁) were measured in SMXA recombinant inbred (RI) strains of mice. For each trait, mean values of substrains of SMXA RI mice showed a continuous spectrum of distribution. A genome-wide linkage test detected QTLs exceeding the suggestive threshold levels for MR of M¹ (chromosomes 1 and 9), PR of M¹ (chromosomes 1, 11 and 19), DR of M¹ (chromosomes 4, 11 and 19) and DR of M₁ (chromosome 11 and 13). These findings suggest that a polygenic system is operative in the determination of tooth root length, and there is some independence of genetic determination among different roots.

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The distribution and morphological features of taste buds in zebrafish (Danio rerio) were investigated with scanning electron (SEM) and light microscopy (LM). The total number of taste buds in zebrafish is approximately 2,200. Taste buds are distributed in almost equal numbers on the external facial skin surface and within the oral cavity, including the gill regions, however, the highest density of taste buds occur along the barbels. Taste buds located on the outer facial skin and within the oral cavity differ in appearance. Those in the oral cavity protrude from the epithelia, whereas those on the external skin surface are sunken. This difference in appearance might be caused by the thickness of the epithelia. The height (30—80 μm) and width (20—50 μm) of taste buds in these two regions are similar, but are of smaller dimensions than those observed in other teleosts. The number (20—23) of cells within a taste bud is less than that reported for other teleost species. The small-sized taste buds and small number of cells may be attributable to the small body size of zebrafish.

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Heating effects on dentin from mammoth tusks were examined by means of X-ray diffraction (XRD) and Fourier transform infrared spectrometric (FTIR), techniques. Dentin samples were sectioned into rectangular plates of about 10×5×1mm in size, using a low speed diamond saw. Heating treatment was carried out using a differential thermal analyzer. It was shown that the organic materials of the dentin were about 32 wt%, and combusted at a temperature range of 200°C to 600°C, showing the coupled exotherm resulting in the release of the inorganic apatite phase from the closely related dentin collagen, and that the exotherm at 700°C related to the crystalline phase transformation from the intermediate phase to crystalline β-TCP. This study suggested that the magnesium components in mammoth tusk dentin manage or control the crystalline phase transformation.

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