title: Glandular and extraglandular expression of costimulatory molecules in patients with Sjögren's syndrome.
abstract: OBJECTIVE
  To investigate the expression and regulation of CD80, CD86, and CD28 costimulatory molecules in sialoadenitis and interstitial nephritis in patients with Sjögren's syndrome (SS).
  
  
  METHODS
  Expression of CD80, CD86, and CD28 molecules was studied by immunohistochemical staining of lip biopsy specimens obtained from patients who had sialoadenitis associated with SS, and renal biopsy specimens obtained from patients who had interstitial nephritis associated with SS. To elucidate the mechanism of de novo expression of CD80 and CD86 antigens, their induction by cytokines in human salivary duct cell line (HSG) and renal cortical epithelial cells (HRCE) by cell enzyme linked immunosorbent assay (ELISA) was quantitatively investigated.
  
  
  RESULTS
  In patients with severe sialoadenitis, CD80 and CD86 were strongly expressed on ductal epithelial cells. In contrast, these antigens were not found in the minor salivary glands of normal subjects or of patients with mild sialoadenitis. Some infiltrating cells expressed CD28. In patients who had interstitial nephritis associated with SS, some tubular epithelial cells expressed CD86 but not the CD80 antigen. Unstimulated HSG cells did not express CD80 or CD86. Interferon gamma (IFNgamma) consistently up regulated levels of CD80 and CD86. In contrast, tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), IL2, and IL4 had no effect on either CD80 or CD86 levels. Unstimulated HRCE did not express CD80 or CD86. IFNgamma consistently up regulated CD86 expression. No CD80 expression was found on tubular cells. TNFalpha, IL1beta, IL2, and IL4 had no discernible effects.
  
  
  CONCLUSIONS
  Salivary ductal cells in patients with SS can express CD80 and CD86 costimulatory molecules in response to IFNgamma. Tubular epithelial cells in patients who have interstitial nephritis associated with SS express only CD86 molecules. In patients with SS, salivary ductal cells and tubular epithelial cells may activate infiltrating CD28 positive T lymphocytes by presenting antigens to T cells, potentially leading to tissue destruction.
authors: Department of Internal Medicine, Toho University School of Medicine, Sakura Hospital, Japan. ryu-ma@ka2.so-net.ne.jp
authors: R
authors: R
authors: Matsumura
authors: K
authors: K
authors: Umemiya
authors: T
authors: T
authors: Goto
authors: T
authors: T
authors: Nakazawa
authors: M
authors: M
authors: Kagami
authors: H
authors: H
authors: Tomioka
authors: E
authors: E
authors: Tanabe
authors: T
authors: T
authors: Sugiyama
authors: M
authors: M
authors: Sueishi
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis*; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000032:analysis; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology*; D008199:Lymphadenitis / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000276:immunology; D012466:Salivary Gland Diseases / Q000276:immunology; D012469:Salivary Glands / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins