Keratinocytes (KCs) may play important roles for maintenance of peripheral tolerance in the upper layers of the skin. Coinhibitory signals mediated via the programmed death (PD)-1 and its ligand B7-H1 (PD-L1/CD274) are crucial for the downregulation of T cell immune responses and for the maintenance of peripheral tolerance. In this study, to investigate the role of KC-expressed B7-H1 in the regulation of T cell immune responses, we generated transgenic (tg) mice overexpressing B7-H1 under the control of keratin 14 (K14) promoter (K14-B7-H1 tg). K14-B7-H1 tg mice displayed impaired contact hypersensitivity (CH) responses to primary and secondary hapten challenges. The K14-B7-H1 tg mice did not exhibit substantial impairment of cutaneous dendritic cell migration after sensitization and of hapten-specific proliferation and IFN-γ production of CD4+ and CD8+ T cells in the draining lymph nodes, suggesting that overexpression of B7-H1 on KCs did not affect the induction phase of the CH response. The systemic or s.c. injection of hapten-sensitized T cells into the K14-B7-H1 tg mice did not efficiently induce the CH response. IFN-γ expression and apoptosis of KCs in the challenged ears were impaired in K14-B7-H1 tg mice. IFN-γ production by presensitized CD8+ T cells stimulated with hapten-pulsed KCs was markedly impaired for the KCs obtained from the K14-B7-H1 tg mice but was restored by the addition of an anti–B7-H1 mAb. These results suggest that KC-associated B7-H1 directly downregulates the effector function of CD8+ T cells by associating with PD-1 at local inflammatory sites and that it plays a role in peripheral T cell tolerance against exogenous Ags.

Summary To investigate the phenotypic and migrational properties of oral mucosal dendritic cells (OMDCs), fluorescein isothiocyanate (FITC) was painted onto mouse buccal mucosa and the expression patterns of functional molecules in FITC‐bearing migrating DCs within the regional lymph nodes (RLNs) were analysed. We found three distinct subpopulations of migrating OMDCs within the RLNs: CD11chi CD207− (F1), CD11cint/lo CD207− (F2) and CD11cint/lo CD207+ (F3). The F1 DCs reached the RLNs earlier (after 24 hr) but diminished immediately. Additionally, F1 DCs expressed high levels of CD11b. The F2 DCs migrated continuously to the RLNs and maintained the highest ratio of all three fractions. The F3 DCs migrated slowly to the RLNs and demonstrated a late peak at 96 hr. In addition, F3 DCs showed the highest CD205 expression levels of all three subsets. All fractions of migrating OMDCs expressed CD80, CD86 and major histocompatibility complex class II at high levels, suggesting that all OMDCs are in a mature stage and have the potential for antigen presentation. All migrating OMDCs lacked CD8α expression. Taken together, our results indicate that the lack of CD207 is one factor that identifies submucosal DCs. Both F1 and F2 DCs lack CD207; F1 DCs are resident and F2 DCs are newly recruited following FITC application. The F3 DCs, which express CD207, are mucosal Langerhans cells that migrate later. The identification of OMDC subsets should facilitate further studies investigating the functional roles of each fraction.

Streptococcus mutans is one of the oral pathogens associated with infective endocarditis (IE).With respect to bacterial binding ability to the extracellular matrix, the Cnm protein, a cell surface collagen-binding adhesin of S. mutans, is known as one of the possible virulence factors with regard to IE. In this study, we aimed to determine the distribution of the cnm gene, which encodes Cnm, in a large number of clinical isolates of S. mutans from Thai subjects. Then, the cnm-positive strains were classified using a multilocus sequence typing (MLST) scheme, which we constructed previously. In addition, the data were analysed together with our previous MLST data of cnmpositive strains from Japan and Finland in order to evaluate the clonal relationship among S. mutans strains harbouring the cnm gene. The cnm gene was detected in 12.4 % of all 750 Thai isolates, and serotype f showed the highest rate of detection (54.5 %). According to the MLST data, two clonal complex groups were revealed as the important clones related to cnm-positive S. mutans from various origins of isolation. Moreover, the collagen-binding properties of S. mutans strains with the cnm gene were significantly greater than those of strains without the gene, although four cnm-negative strains classified into two sequence types (STs), ST110 and ST136, showed extremely high collagen-binding rates suggesting the presence of additional genes involved with collagen binding in these STs. Taken together, these results provided information on both epidemiological as well as evolutional aspects of S. mutans possessing the cnm gene. INTRODUCTIONStreptococcus mutans is a well-known pathogen of dental caries (Hamada & Slade, 1980), which consists of four serotypes, c, e, f and k (Linzer et al., 1986;). The detection rate of serotype c is highest among the strains isolated from oral cavities, followed by serotype e, while serotypes f and k are regarded as being present in minor proportions . Various pieces of evidence show the association of S. mutans with some life-threatening diseases such as infective endocarditis (IE), although the major species related to IE belong to the mitis group of oral streptococci (Banas, 2004;Mylonakis & Calderwood, 2001). Moreover, continuous detections of this bacterium in specimens from patients suffering from such disease emphasize the importance of S. mutans in IE (Gauduchon et al., 2001;Nomura et al., 2006;Vose et al., 1987;Ullman et al., 1988). Indeed, studies to clarify specific components involved in IE in S. mutans have also been performed worldwide (Beg et al., 2002;Jung et al., 2009; MatsumotoNakano et al., 2009;Miller-Torbert et al., 2008).IE is initiated by the binding of bacterial surface molecules to host extracellular matrix (ECM) proteins exposed on damaged heart tissue (Moreillon & Que, 2004). In S. mutans, collagen-binding adhesin or Cnm protein, encoded by the cnm gene, was reported as a strain-specific collagen-binding molecule (Sato et al., 2004). The Cnm protein possesses a collagen-binding domain (CBD) in ...

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