Abstract: CD4+ PD-1+ T Cells Accumulate as Unique Anergic Cells in Rheumatoid Arthritis Synovial Fluid

CD4+ PD-1+ T Cells Accumulate as Unique Anergic Cells in Rheumatoid Arthritis Synovial Fluid

SAORI HATACHI, YOSHIKO IWAI, SEIJI KAWANO, SAHOKO MORINOBU, MASAYA KOBAYASHI, MASAHIRO KOSHIBA, RYUICHI SAURA, MASAHIRO KUROSAKA, TASUKU HONJO, and SHUNICHI KUMAGAI

ABSTRACT.

Objective. The PD-1 receptor, whose deficiency in mice causes autoimmune diseases such as arthritis, is considered to be a negative regulator of activated T cells and to play a crucial role in peripheral tolerance. To clarify the involvement of the PD-1 system in rheumatoid arthritis (RA), we investigated PD-1 expression on synovial fluid (SF) T cells from patients with RA.

Methods. FACS analysis for PD-1 was performed on SF T cells from 44 patients with RA and 6 with osteoarthritis (OA), and also on peripheral blood (PB) T cells from 12 RA patients and 7 healthy controls. Two-color analysis of cell surface PD-1 expression and the intracellular concentration of cytokine production was used to investigate CD4+ T cells from SF of patients with RA and PB from controls.

Results. Scarcely any PD-1 expression was detected on control PB T or OA SF T cells. In contrast, PD-1+ cells made up 20.9 ± 8.6% (mean ± SD) of RA SF T cells. In RA SF, PD-1 was expressed more predominantly on CD4+ T cells than on CD8+ T cells. As well as expressing CD45RO and CXCR3, CD4+ PD-1+ T cells were mostly CTLA-4 positive and CD26 negative, and were enriched in CD45RB^low cells. Intracellular cytokine staining revealed that CD4+ PD-1+, but not CD4+ PD-1–, T cells produced interleukin 10 (IL-10), and that CD4+ PD-1+ T cells produced less IL-2 than CD4+ PD-1– T cells.

Conclusion. PD-1+ T cells in RA SF are enriched, and phenotypic analysis suggests that these cells constitute a unique anergic T cell subset in RA SF. (J Rheumatol 2003;30:1410-9)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
SYNOVIAL FLUID
T CELLS
FLOW CYTOMETRY
PD-1

From the Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, Kobe, Japan.

Supported by a Grant-in-Aid for Scientific Research (14370164) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

S. Hatachi, MD; S. Kawano, MD, PhD; S. Morinobu, MD; M. Kobayashi, MS; M. Koshiba, MD, PhD; S. Kumagai, MD, PhD, Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine; Y. Iwai, MD; T. Honjo, MD, PhD, Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto; R. Saura, MD, PhD; M. Kurosaka, MD, PhD, Department of Orthopedics, Kobe University Graduate School of Medicine.

Address reprint requests to Dr. S. Kumagai, Department of Clinical Pathology and Immunology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. E-mail: kumagais@kobe-u.ac.jp

Submitted September 24, 2002; revision accepted December 31, 2002.