title: Direct infection of primary salivary gland epithelial cells by human T lymphotropic virus type I in patients with Sjögren's syndrome.
abstract: OBJECTIVE
  To investigate whether human T lymphotropic virus type I (HTLV-I) directly infects salivary gland epithelial cells (SGECs) and induces the niche of the salivary glands in patients with Sjögren's syndrome (SS).
  
  
  METHODS
  SGECs were cultured with the HTLV-I-producing CD4+ T cell line HCT-5 or with Jurkat cells. Antibody arrays, immunofluorescence analysis, and enzyme-linked immunosorbent assay (ELISA) were used to determine the profiles of inflammation-related molecules, and the profiles of apoptosis-related molecules were determined by antibody array and immunofluorescence analysis. The presence of HTLV-I-related molecules was assessed by immunofluorescence analysis and in situ polymerase chain reaction. Apoptosis of SGECs was evaluated by TUNEL staining.
  
  
  RESULTS
  Among the SGECs, 7.8 ± 1.3% (mean ± SD) were positive for HTLV-I-related proteins after 96-hour coculture with HCT-5 cells. Nuclear NF-κB p65 was also detected in 10% of the SGECs. The presence of HTLV-I proviral DNA in SGECs after coculture with HCT-5 cells was detected by in situ polymerase chain reaction. After coculture of SGECs with HCT-5, the expression of cytokines and chemokines, including soluble intercellular adhesion molecule 1, RANTES, and interferon γ-induced protein 10 kd (IP-10/CXCL10) was increased in a time-dependent manner. The expression of proapoptotic molecules (e.g., cytochrome c and Fas) and antiapoptotic molecules (e.g., Bcl-2, Heme oxygenase 2, and Hsp27) was increased in the SGECs cocultured with HCT-5, showing that apoptosis of SGECs was not detected after coculture with HCT-5 or Jurkat cells.
  
  
  CONCLUSIONS
  HTLV-I is thought to infect SGECs and alter their cellular functions. These changes may induce the niche of SS and contribute to the development of SS in anti-HTLV-I antibody-positive individuals.
authors.affiliation: Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamamoto-Fukuda
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Horai
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nakashima
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Arima
authors.forename: Tatsufumi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawakami
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology*; D005260:Female; D015368:Human T-lymphotropic virus 1; D006801:Humans; D008875:Middle Aged; D012469:Salivary Glands / Q000378:metabolism / Q000821:virology*; D012859:Sjogren's Syndrome / Q000378:metabolism / Q000821:virology*
chemical_list: D018925:Chemokines; D016207:Cytokines