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Expression and Function of the Co-Stimulator H4/ICOS on Activated T Cells of Patients with Rheumatoid Arthritis
TOSHIHIRO OKAMOTO, SEIJI SAITO, HISASHI YAMANAKA, TAISUKE TOMATSU, NAOYUKI KAMATANI, HIDEKI OGIUCHI, TAKEHIKO UCHIYAMA, and JUNJI YAGI
ABSTRACT. Objective. To investigate the expression and function of the inducible co-stimulator H4/ICOS in rheumatoid arthritis (RA) patients. H4/ICOS is the newest member of the CD28/CTLA-4 family to have been found to be expressed on activated T cells, and it participates in a variety of important immunoregulatory functions. Methods. The levels of H4/ICOS expression on T cells among peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) from 28 patients with RA were analyzed by flow cytometry. To explore the role of H4/ICOS function in the inflammation of rheumatoid joints, lymphokine production by SF CD4+ T cells co-stimulated by H4/ICOS was assayed. Expression of H4/ICOS ligand (B7RP-1) mRNA in synovial tissues from patients with RA was examined by reverse transcription polymerase chain reaction (RT-PCR). Results. H4/ICOS-positive cells were increased significantly in whole, CD4+, and CD8+ T-cell fractions of SFMC compared with control PBMC. Comparison between control PB and PB from patients with active RA showed that H4/ICOS-positive whole and CD8+ T-cell fractions were increased significantly in the PB of RA patients. H4/ICOS costimulation clearly increased interferon-g, interleukin 4 (IL-4), and IL-10 production by SF CD4+ T cells. By RT-PCR, RA synovial tissue was shown to express mRNA of B7RP-1. Conclusion. Our results suggest that local immune responses may be modulated by H4/ICOS expressed on T cells in the joints of patients with RA, and thus H4/ICOS may be involved in the pathogenetic mechanism of RA. (J Rheumatol 2003;30:1157–63) Key Indexing Terms:
T LYMPHOCYTES
From the Department of Oral and Maxillofacial Surgery, the Institute of Rheumatology, and the Department of Microbiology and Immunology, Tokyo Women's Medical University, Tokyo, Japan. Supported in part by grants from the Ministry of Education, Science, Sports and Culture of Japan, and the Ministry of Public Welfare of Japan. T. Okamoto, DDS, Research Associate, Department of Oral and Maxillofacial Surgery and Department of Microbiology and Immunology; H. Ogiuchi, DDS, PhD, Professor, Department of Oral and Maxillofacial Surgery; S. Saito, MD, PhD, Associate Professor; H. Yamanaka, MD, PhD, Associate Professor; T. Tomatsu, MD, PhD, Professor; N. Kamatani, MD, PhD, Director; Institute of Rheumatology; T. Uchiyama, MD, PhD, Professor, Director, Department of Microbiology and Immunology and Institute of Laboratory Animals; J. Yagi, MD, PhD, Assistant Professor, Department of Microbiology and Immunology. Address reprint requests to Dr. T. Okamoto, Department of Oral and Maxillofacial Surgery, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. E-mail: okamoto@oms.twmu.ac.jp Submitted February 26, 2002; revision accepted December 19, 2002. |