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Possible Function of Salivary Gland Epithelial Cells as Nonprofessional Antigen-Presenting Cells in the Development of Sjögren's Syndrome
SHIZUKA TSUNAWAKI, SEIJI NAKAMURA, YUKIKO OHYAMA, MASANORI SASAKI, AKIKO IKEBE-HIROKI, AKIMITSU HIRAKI, TSUTOMU KADENA, EIJI KAWAMURA, WATARU KUMAMARU, MASANORI SHINOHARA, and KANEMITSU SHIRASUNA
ABSTRACT.
Methods. Expression of HLA-DR antigens, costimulatory molecules, and adhesion molecules on epithelial cells was immunohistochemically examined in labial salivary glands from patients with SS. An association with the expression of T cell derived cytokine messenger RNA (mRNA) was observed. The expression of these molecules was confirmed using cultured salivary gland epithelial cells. The ability of the salivary gland epithelial cells as nonprofessional APC was examined in a mixed culture system using the salivary gland epithelial cells and allogeneic lymphocytes. Results. Expression of HLA-DR antigens, CD80, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM), and E-selectin was immunohistochemically detected on duct cells from all patients; however, the expression of CD86 was limited to only some patients. Concomitant expression of CD80 on duct cells and Th1 cytokine mRNA, and CD86 on duct cells and Th2 cytokine mRNA, was observed. Interferon-g (IFN-g) induced the cultured salivary gland epithelial cells to express HLA class I antigens, HLA-DR antigens, CD80, and ICAM-1, while tumor necrosis factor-a (TNF-a) induced the expression of HLA class I antigens, CD80, CD86, and VCAM. Cultured salivary gland epithelial cells treated with either IFN-g or TNF-a also caused allogeneic lymphocytes to proliferate. Conclusion. The ability of salivary gland epithelial cells to express HLA-DR antigens, costimulatory molecules, and adhesion molecules and thus to act as nonprofessional APC was suggested. CD80 and CD86 expression of these cells was also suggested to be involved in the activation of Th1 and Th2, respectively. (J Rheumatol 2002;29:1884-96) Key Indexing Terms:
SJÖGREN'S SYNDROME
From the Department of Oral and Maxillofacial Surgery, Graduate School of Dental Science, Kyushu University, Fukuoka; and the Department of Oral and Maxillofacial Surgery, School of Medicine, Kumamoto University, Kumamoto, Japan. Supported in part by grants from the Ministry of Education, Science, and Culture of Japan. S. Tsunawaki, DDS; S. Nakamura, DDS, PhD; Y. Ohyama, DDS, PhD; M. Sasaki, DDS, PhD; A. Ikebe-Hiroki, DDS, PhD; A. Hiraki, DDS; T. Kadena, DDS, PhD; E. Kawamura, DDS; W. Kumamaru, DDS; K. Shirasuna, DDS, PhD, Department of Oral and Maxillofacial Surgery, Graduate School of Dental Science, Kyushu University; M. Shinohara, DDS, PhD, Department of Oral and Maxillofacial Surgery, School of Medicine, Kumamoto University. Address reprint requests to Dr. S. Nakamura, Department of Oral and Maxillofacial Surgery, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail: seiji@dent.kyushu-u.ac.jp Submitted February 16, 2001; revision accepted March 8, 2002.
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