Constitutive expression of 4-1BB on T cells enhances CD4+ T cell responses

4-1BB, a transmembrane molecule, member of the tumor necrosis factor receptor superfamily, is an im portant costim ulatory molecule in the immune response, plays a key role in the clonal expansion and survival of CD8+ T cells. In this study, we investigated 4-1BB regulation of CD4+ T cell responses using 4-1BB transgenic (TG) mice that constitutively expressed 4-1BB on mature T cells. We first showed that CD4+ T cells of 4-1BB TG mice had more sustained proliferative capacity in response to TCR/4-1BB stimulation in vitro compared to WT mice. Secondly, 4-1BB TG mice exhibited a more elevated contact hypersensitivity (CHS) response mediated by CD4+ Th1 cells due to more vigorous expansion of and apoptotic inhibition of CD4+ T cells. Finally, CD4+ T cells of 4-1BB TG mice had a heightened capacity for T cell prim ing. Overall, our results demonstrate the involvement of 4-1BB in CD4+ Th1 cell responses by regulating the clonal expansion and survival of CD4+ T cells as seen in CD8+ T cells.This work was supported by Korea Research Foundation Grant (KRF2000-D00285)

High levels of soluble herpes virus entry mediator in sera of patients with allergic and autoimmune diseases

Herpes virus entry mediator (HVEM) is a newly discovered member of the tumor necrosis factor receptor (TNFR) superfamily that has a role in herpes simplex virus entry, in T cell activation and in tumor immunity. We generated mAb against HVEM and detected soluble HVEM (SHVEM) in the sera of patients with various autoimmune diseases. HVEM was constitutively expressed on CD4+ and CD8+ T cells, CD19+ B cells, CD14+ monocytes, neutrophils and dendritic cells. In three-way MLR, mAb 122 and 139 were agonists and mAb 108 had blocking activity. An ELISA was developed to detect sHVEM in patient sera. sHVEM levels were elevated in sera of patients with allergic asthma, atopic dermatitis and rheumatoid arthritis. The mAbs discussed here may be useful for studies of the role of HVEM in immune responses. Detection of soluble HVEM might have diagnostic and prognostic value in certain immunological disorders

Upregulation of Intercellular Adhesion Molecule 1 and Proinflammatory Cytokines by the Major Surface Proteins of Treponema maltophilum and Treponema lecithinolyticum, the Phylogenetic Group IV Oral Spirochetes Associated with Periodontitis and Endodontic Infections

Treponema maltophilum and Treponema lecithinolyticum belong to the group IV oral spirochetes and are associated with endodontic infections, as well as periodontitis. Recently, the genes encoding the major surface proteins (Msps) of these bacteria (MspA and MspTL, respectively) were cloned and sequenced. The amino acid sequences of these proteins showed significant similarity. In this study we analyzed the functional role of these homologous proteins in human monocytic THP-1 cells and primary cultured periodontal ligament (PDL) cells using recombinant proteins. The complete genes encoding MspA and MspTL without the signal sequence were cloned into Escherichia coli by using the expression vector pQE-30. Fusion proteins tagged with N-terminal hexahistidine (recombinant MspA [rMspA] and rMspTL) were obtained, and any possible contamination of the recombinant proteins with E. coli endotoxin was removed by using polymyxin B-agarose. Flow cytometry showed that rMspA and rMspTL upregulated the expression of intercellular adhesion molecule 1 (ICAM-1) in both THP-1 and PDL cells. Expression of proinflammatory cytokines, such as interleukin-6 (IL-6) and IL-8, was also induced significantly in both cell types by the Msps, as determined by reverse transcription-PCR and an enzyme-linked immunosorbent assay, whereas IL-1β synthesis could be detected only in the THP-1 cells. The upregulation of ICAM-1, IL-6, and IL-8 was completely inhibited by pretreating the cells with an NF-κB activation inhibitor, l-1-tosylamido-2-phenylethyl chloromethyl ketone. This suggests involvement of NF-κB activation. The increased ICAM-1 and IL-8 expression in the THP-1 cells obtained with rMsps was not inhibited in the presence of the IL-1 receptor antagonist (IL-1ra), a natural inhibitor of IL-1. Our results show that the Msps of the group IV oral spirochetes may play an important role in amplifying the local immune response by continuous inflammatory cell recruitment and retention at an infection site by stimulation of expression of ICAM-1 and proinflammatory cytokines

Cloning and sequence analysis of the gene encoding the crystalline surface layer protein of Rickettsia typhi

The nucleotide sequence of the gene (slp7) encoding the crystalline surface layer protein (SLP) of Rickettsia typhi was determined. The slpTgene consists of 4935 bp coding for a 1645-amino-acid (aa) protein containing a predicted signal peptide at the N terminus. The size of the predicted SLP exceeds the observed size (135 kDa) on SDS-PAGE. The N-terminal aa sequence of the 32-kDa protein of R. typhi reported by Hackstadt et al. [Infect. Immun. 60 (1992) 159-1651 was found in the C-terminal portion of the deduced aa sequence, suggesting that the product of slpT is processed into the mature SLP and the 32-kDa protein.This work was supported by Basic Medical Science Research fund from the Ministry of Education, Korea 1993

Effects of Subinhibitory Antibiotic Concentrations on Porphyromonas gingivalis Fibrinogen and Hemin Binding

Porphllromonas gingivalis, a gram-negative anaerobe, is one of the major causative agents in periodontal disease In this study, the effect of sub-inhibitory concentrations of antibiotics on the binding characteristics of P, g ngivalis was examined. P. gingivalis strains 381 and W50 were grown in broth containing one-half the m: nimum inhibitory concentration (MIC) of amoxicillin, doxycycline, metronidazole, penicillin, or tetracycline. Surface hydrophobicity, fibrinogen binding (soluble and immobilized) and hemin binding were evalua :ed. The surface hydrophobicity of strain 381 cultured in each antibiotic decreased, whereas strain W50 showed no statistically significant changes in surface hydrophobicity. All antibiotics used decreased soluble: fibrinogen binding of strain 381. In contrast, all antibiotics, except penicillin, increased binding of soluble: fibrinogen for strain W50. Binding of strain 381 to immobilized fibrinogen increased in the presence of amc iacillin and doxycycline; the binding of strain W50 to immobilized fibrinogen was not affected by any antibic tic. Hemin binding of strain 381 was unaltered by any antibiotic, whereas hemin binding by strain W50 was increased by amoxicillin, metronidazole and penicillin. These observations showed that sub-inhibitory concentrations of antibiotics could confer variable effects on the binding properties of P. gingivalis

Synergistic inhibitory effect of cationic peptides and antimicrobial agents on the growth of oral streptococci

Although chlorhexidine is one of the most efficacious antimicrobial agents used for the prevention of dental caries, side effects limit its application. The effects of gaegurin 6 (GGN6), an animal-derived cationic peptide, and its derivatives PTP6 and PTP12 on the growth of oral streptococci were investigated to assess the potential of these agents for use in the prevention of dental caries. The minimal inhibitory concentrations of the peptides for inhibition of the growth of oral streptococci <(Streptococcus mutans, S. sobrinus, S. sanguis <and <S. gordonii)< ranged from 1.2 to 8.2 [mu]<M<. The peptides also exhibited marked synergistic antibacterial effects with chlorhexidine or xylitol. The most effective combinations (fractional inhibitory concentration index of 0.5) were xylitol with GGN6 against <S. gordonii <10558 and chlorhexidine with either GGN6 or PTP6 against <S. sobrinus <OMZ-175. These results indicate that cationic peptides alone or in combination with chlorhexidine or xylitol might prove effective for the inhibition of the growth of cariogenic oral streptococci in situ

BioLattice: a framework for the biological interpretation of microarray gene expression data using concept lattice analysis

MOTIVATION: A challenge in microarray data analysis is to interpret observed changes in terms of biological properties and relationships. One powerful approach is to make associations of gene expression clusters with biomedical ontologies and/or biological pathways. However, this approach evaluates only one cluster at a time, returning long unordered lists of annotations for clusters without considering the overall context of the experiment under investigation. RESULTS: BioLattice is a mathematical framework based on concept lattice analysis for the biological interpretation of gene expression data. By considering gene expression clusters as objects and associated annotations as attributes and by using set inclusion relationships BioLattice orders them to create a lattice of concepts, providing an 'executive' summary of the experimental context. External knowledge resources such as Gene Ontology trees and pathway graphs can be added incrementally. We propose two quantitative structural analysis methods, 'prominent sub-lattice' and 'core-periphery' analyses, enabling systematic comparison of experimental concepts and contexts. BioLattice is implemented as a web-based utility using Scalable Vector Graphics for interactive visualization. We applied it to real microarray datasets with improved biological interpretations of the experimental contexts

Establishment of a dental license regulation authority is required in Korea: results of the Delphi technique

Purpose In addition to dental education, a system for the evaluation and management of dental licensing and certification is required to meet the growing societal demand for more competent dentists. In this study, the Delphi technique was used to gather opinions from a variety of professionals on the problems of and remedies for the dental license management system in Korea. Methods Delphi surveys were conducted from April 2016 to October 2016 in South Korea. A variety of dental professionals were included and categorized into 3 groups according to their expertise as follows: the basic dentistry group, the clinical dentistry group, and the policy group. The Delphi technique was conducted in 3 rounds of e-mail surveys, each with different questions that probed with increasing depth on the dental license management system. In each successive round, the responses were categorized, scored on a Likert scale, and statistically analyzed. Results After categorizing the results of the first survey and ranking the results of the second survey using the Delphi technique, regulation by a licensing authority was found to be the most critical issue. This was followed by the license renewal system, continuing education, a tiered licensure system, improvement of foreign license approval, and utilization of retirees, in decreasing order of importance. The third Delphi survey showed a similar ranking, with regulation by a licensing authority being the major concern. Opinions regarding the dental license management system were provided as open-ended responses. The responses of the 3 groups showed statistically significant differences in the scores for the issue of regulation by a licensing authority. After re-grouping into the dentistry group and the policy group, the issue received a significantly higher score in the dentistry group. Conclusion The quality of dental treatment should be managed to protect patients and dental professionals. For this purpose, the establishment of an independent license regulation authority along with legislative changes is required