Journal Article Direct Infection of Primary Salivary Gland Epithelial Cells by Human T Lymphotropic Virus Type I in Patients With Sjögren's Syndrome

Nakamura, Hideki  ,  Takahashi, Yoshiko  ,  Yamamoto-Fukuda, Tomomi  ,  Horai, Yoshiro  ,  Nakashima, Yoshikazu  ,  Arima, Kazuhiko  ,  Nakamura, Tatsufumi  ,  Koji, Takehiko  ,  Kawakami, Atsushi

67 ( 4 )  , pp.1096 - 1106 , 2015-04 , John Wiley and Sons Ltd
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. Conclusion 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.

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