title: Characterization of effector memory CD8+ T cells in the synovial fluid of rheumatoid arthritis.
abstract: Little is known about the cellular characteristics of CD8(+) T cells in rheumatoid arthritis (RA). We addressed this by investigating whether the frequency of the CD8(+) T cell subsets and their phenotypic characteristics are altered in the peripheral blood and synovial fluid (SF) from patients with RA. In this study, CD8(+) T cells, mainly CD45RA(-) effector memory (EM) CD8(+) T cells, were increased significantly in the SF, but not in the peripheral blood from RA patients, compared with healthy controls. The synovial EM CD8(+) T cells were activated phenotypes with high levels of CD80, CD86, and PD-1, and had a proliferating signature in vivo upon Ki-67 staining, whereas the Fas-positive cells were prone to apoptosis. In addition, EM CD8(+) T cells in the SF were less cytotoxic, as they expressed less perforin and granzyme B. In particular, the proportions of synovial fluid mononuclear cells that were CCR4(+)CD8(+) T cells and IL-4-producing CD8(+) T cells (i.e., Tc2 cells) were significantly higher than those in peripheral blood mononuclear cells of patients with RA and healthy controls. In addition, the number of IL-10-producing CD8(+) suppressor T (Ts) cells increased significantly in the SF of RA patients. Especially, CD8(+) T cells were inversely correlated with disease activity. These findings strongly suggest that EM CD8(+) T cells in the SF are increased, likely because of inflammation, and they may be involved in modulating inflammation, thereby affecting the development and progression of RA.
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Republic of Korea.
authors.forename: Bon-A
authors.initials: BA
authors.lastname: Cho
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Sim
authors.forename: Ji Ah
authors.initials: JA
authors.lastname: Park
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Kim
authors.forename: Wan-Hee
authors.initials: WH
authors.lastname: Yoo
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Dong-Sup
authors.initials: DS
authors.lastname: Lee
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kang
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Hwang
authors.forename: Wang Jae
authors.initials: WJ
authors.lastname: Lee
authors.forename: Insoo
authors.initials: I
authors.lastname: Kang
authors.forename: Eun Bong
authors.initials: EB
authors.lastname: Lee
authors.forename: Hang-Rae
authors.initials: HR
authors.lastname: Kim
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology*; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D053804:Granzymes / Q000096:biosynthesis; D006801:Humans; D007156:Immunologic Memory; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000096:biosynthesis; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis; D013582:Synovial Fluid / Q000276:immunology*
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D054353:Perforin; D016753:Interleukin-10; D015847:Interleukin-4; D053804:Granzymes