Selective recruitment of CXCR3+ and CCR5+ CCR4+ T cells into synovial tissue in patients with rheumatoid arthritis.
The inflamed synovial tissue (ST) of rheumatoid arthritis (RA) is characterized by the selective accumulation of interferon gamma-producing Th1-type CD4+ T cells. In this study, we investigated whether the predominance of Th1-type CD4+ cells in the ST lesion is mediated by their selective recruitment through Th1 cell-associated chemokine receptors CXCR3 and CCR5. The lymphocyte aggregates in the ST of RA contained a large number of CD4+ T cells, which mostly expressed both CXCR3 and CCR5, but not CCR4. In contrast, the frequencies of CD4+ and CD8+ T cells expressing CXCR3 and CCR5 in the blood were significantly decreased in RA patients, compared with healthy controls (HC), although there was no difference in the frequencies of CCR4-expressing CD4+ and CD8+ T cells between RA and HC. CXCR3, CCR5, and CCR4 expression in blood CD4 + T cells and CXCR3 expression in CD8+ T cells were increased after interleukin-15 (IL-15) stimulation. Therefore, the distribution of Th1-type CD4+ T cells into the ST from the blood in RA may be associated with the local expression of chemokines, both CXCR3 and CCR5 ligands, and IL-15 may play a role in enhancing these chemokine receptors on CD4+ T cell infiltrates.
Norii
Mika
M
Department of Medicine and Clinical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Yamamura
Masahiro
M
Iwahashi
Mitsuhiro
M
Ueno
Akiko
A
Yamana
Jiro
J
Makino
Hirofumi
H
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000503:physiopathology*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry* / Q000276:immunology / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D016022:Case-Control Studies; D002465:Cell Movement / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019409:Interleukin-15 / Q000502:physiology; D008024:Ligands; D008297:Male; D008875:Middle Aged; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000378:metabolism*; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis / Q000378:metabolism*; D013583:Synovial Membrane / Q000276:immunology* / Q000503:physiopathology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology
C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D019409:Interleukin-15; D008024:Ligands; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine