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(Chest. 2005;128:2497-2503.)
© 2005 American College of Chest Physicians

Enhanced Expression of Interleukin-18 Receptor {alpha} Chain by CD4+ T Cells in Sarcoidosis*

Yanqiu Zhou, MD; Etsuro Yamaguchi, MD; Yoshinobu Fukui, MD; Satoshi Konno, MD; Yukiko Maeda, MD; Koji Kimata, PhD and Masaharu Nishimura, MD

* From the Department of Respiratory Medicine (Drs. Zhou, Fukui, Konno, Maeda, and Nishimura), Graduate School of Medicine, Hokkaido University, Sapporo; and Division of Respiratory Medicine and Allergology (Dr. Yamaguchi), Department of Internal Medicine, and Institute for Molecular Science of Medicine (Dr. Kimata), Research Center for Infectious Disease, Aichi Medical University, Aichi, Japan.

Correspondence to: Etsuro Yamaguchi, MD, Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Aichi Medical University School of Medicine, Yazako Karimat 21, Nagakute, Aichi, 480-1195, Japan; e-mail: etsuro{at}aichi-med-u.ac.jp

Study objectives: To investigate the expression of interleukin-18 receptor {alpha} chain (IL-18R{alpha}) in BAL and peripheral blood (PB) T cells in patients with sarcoidosis compared with control subjects, to evaluate the relationship between the expression and clinical manifestations, and to clarify the mechanisms of altered expression.

Subjects and methods: The study subjects consisted of 21 patients with sarcoidosis and 8 normal control subjects. The expression of IL-18R{alpha} was examined by flow cytometry.

Results: The proportions of BAL CD4+ and PB CD4+ T cells expressing IL-18R{alpha} were significantly increased in patients with sarcoidosis compared to control subjects. BAL CD4+ T cells expressed IL-18R{alpha} in a higher proportion than did paired CD8+ T cells in patients with sarcoidosis but not in control subjects. Greater proportions of BAL CD4+ T cells and BAL CD8+ T cells than of their PB counterparts expressed IL-18R{alpha} in both patients and control subjects. CD4+ T cells were more sensitive to the induction of IL-18R{alpha} by cytokines in vitro, such as interleukin (IL)-2, IL-12, and tumor necrosis factor-{alpha} than were CD8+ T cells. Increased expression of IL-18R{alpha} by BAL T cells commonly observed in patients and control subjects was associated with the expansion of CD45RO+ cells in BAL T cells. However, there were no significant correlations between the expression of IL-18R{alpha} by any cell populations and BAL findings, serum angiotensin-converting enzyme activities, radiograph stages, or clinical courses.

Conclusion: The overexpression of IL-18R{alpha} predominantly by CD4+ T cells in sarcoidosis emphasizes crucial roles played by T-helper type 1 cells in the IL-18/IL-18R{alpha} system in sarcoidosis.

Key Words: BAL • CD4+ T cell • interleukin-18 • interleukin-18 receptor {alpha} chain






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