Requirement of B7 costimulation for Th1-mediated inflammatory bone resorption in experimental periodontal disease.

Abstract	The CD28 costimulation at TCR signaling plays a pivotal role in the regulation of the T cell response. To elucidate the role of T cells in periodontal disease, a system of cell transfer with TCR/CD28-dependent Th1 or Th2 clones was developed in rats. Gingival injection of specific Ag, Actinobacillus actinomycetemcomitans 29-kDa outer membrane protein, and LPS could induce local bone resorption 10 days after the transfer of Ag-specific Th1 clone cells, but not after transfer of Th2 clone cells. Interestingly, the presence of LPS was required not only for the induction of bone resorption but also for Ag-specific IgG2a production. LPS injection elicited the induction of expression of both B7-1 and B7-2 expression on gingival macrophages, which otherwise expressed only MHC class II when animals were injected with Ag alone. The expression of B7 molecules was observed for up to 3 days, which corresponded to the duration of retention of T clone cells in gingival tissues. Either local or systemic administration of CTLA4Ig, a functional antagonist of CD28 binding to B7, could abrogate the bone resorption induced by Th1 clone cells combined with gingival challenge with both Ag and LPS. These results suggest that local Ag-specific activation of Th1-type T cells by B7 costimulation appeared to trigger inflammatory bone resorption, whereas inhibition of B7 expression by CTLA4Ig might be a therapeutic approach for intervention with inflammatory bone resorption.
Authors	T Kawai, R Eisen-Lev, M Seki, J W Eastcott, M E Wilson, M A Taubman
Journal	Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 164 Issue 4 Pg. 2102-9 (Feb 15 2000) ISSN: 0022-1767 [Print] United States
PMID	10657664 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Antigens, CD Antigens, Differentiation B7-1 Antigen B7-2 Antigen CD86 protein, human CTLA-4 Antigen CTLA4 protein, human Cd86 protein, rat Ctla4 protein, rat Histocompatibility Antigens Class II Immunoconjugates Immunoglobulin G Isoenzymes Lipopolysaccharides Membrane Glycoproteins RNA, Messenger Abatacept Acid Phosphatase Tartrate-Resistant Acid Phosphatase
Topics	Abatacept Acid Phosphatase (biosynthesis) Alveolar Bone Loss (enzymology, pathology) Animals Antigens, CD (biosynthesis) Antigens, Differentiation (administration & dosage, therapeutic use) B7-1 Antigen (administration & dosage, genetics, physiology) B7-2 Antigen Bone Resorption (enzymology, immunology, pathology, prevention & control) CTLA-4 Antigen Clone Cells (immunology, transplantation) Female Gingiva (cytology, immunology) Histocompatibility Antigens Class II (biosynthesis) Humans Immunoconjugates Immunoglobulin G (biosynthesis) Injections, Intravenous Isoenzymes (biosynthesis) Kinetics Lipopolysaccharides (administration & dosage) Lymph Nodes (cytology, immunology) Macrophages (immunology, metabolism) Membrane Glycoproteins (biosynthesis) Microinjections Neck Periodontitis (enzymology, immunology, pathology) RNA, Messenger (biosynthesis) Rats Rats, Inbred Strains Spleen (cytology, immunology) Tartrate-Resistant Acid Phosphatase Th1 Cells (immunology, transplantation) Th2 Cells (transplantation)

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