title: Individual diversities in interferon gamma production by human peripheral blood mononuclear cells stimulated with periodontopathic bacteria.
abstract: Polarization of type 1 (Th1) or type 2 (Th2) immune responses determines the prognosis of many infectious diseases. Interferon gamma (IFN-gamma) and IL-4 are key cytokines for the development of type 1 and type 2 immune responses, respectively. The aim of this study was to examine individual diversities in the polarization of type 1 and type 2 responses against periodontopathic bacteria. Peripheral blood mononuclear cells (PBMCs) from adult periodontitis (AP) patients and healthy (H) subjects were stimulated with Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Bacteroides forsythus with or without polymyxin-B, CTLA-4 Ig and anti-IL-12 antibody. IFN-gamma, IL-4 and IL-12 in the culture supernatant were measured. IFN-gamma and IL-4 producing cells were also examined using a multiparameter flow cytometric assay. Bone resorption rate in AP patients was calculated using Schei's method, and the probing pocket depth was also measured. PBMCs from AP patients and H subjects produced IFN-gamma and IL-12, whereas the production of IL-4 was rarely observed. Among the bacteria tested, A. actinomycetemcomitans was the most potent inducer of IFN-gamma and IL-12, and the reaction was inhibited by polymyxin-B. IFN-gamma was found to be produced by T cells in the PBMCs, and the production was significantly reduced by CTLA-4 Ig and anti-IL-12 neutralizing antibody. The amount of IFN-gamma produced by the PBMCs of AP patients and H subjects varied among individuals, and was significantly correlated with the amount of IL-12 produced in a particular individual. The production of IFN-gamma was not related with periodontal condition which was evaluated using bone resorption and pocket depth. These results suggest that polarization of type 1 response against periodontopathic bacteria is dependent on the production of IL-12 by monocytes, and that IL-12 stimulates IFN-gamma production. However, individual diversities of IFN-gamma production might not be directly related to the severity of periodontitis.
authors.affiliation: Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Japan. h-kobayashi.peri@tmd.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Nagasawa
authors.forename: M
authors.initials: M
authors.lastname: Aramaki
authors.forename: R
authors.initials: R
authors.lastname: Mahanonda
authors.forename: I
authors.initials: I
authors.lastname: Ishikawa
mesh_terms: D000328:Adult; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D001439:Bacteroides / Q000276:immunology; D005434:Flow Cytometry; D014644:Genetic Variation; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics*; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000276:immunology; D009000:Monocytes / Q000378:metabolism; D010518:Periodontitis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000276:immunology; D018709:Statistics, Nonparametric; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma