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

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.