CCR3, CCR5, interleukin 4, and interferon-gamma expression on synovial and peripheral T cells and monocytes in patients with rheumatoid arthritis.
OBJECTIVE
To characterize cytokine and chemokine receptor profiles of T cells and monocytes in inflamed synovium and peripheral blood (PB) in patients with rheumatoid arthritis (RA) and other arthritides.


METHODS
We studied PB and synovial fluid (SF) samples taken from 20 patients with RA and 9 patients with other arthritides. PB cells from 8 healthy adults were used as controls. CCR3, CCR5, and intracellular interferon-g (IFN-g) and interleukin 4 (IL-4) expression in CD8+ and CD8- T cell populations and in CD14+ cells were determined with flow cytometry.


RESULTS
Expression of CCR5 and CCR3 by CD8-, CD8+ T cells and CD14+ monocytes was increased in SF compared to PB cells in patients with RA and other arthritides. The number of CD8+ T cells spontaneously expressing IL-4 and IFN-g was higher in SF than in PB in RA patients. Spontaneous CCR5 expression was associated with intracellular IFN-g expression in CD8+ T cells derived from SF in RA. In CD8- T cells the ratio of CCR5+/CCR3+ cells was increased in patients with RA compared to patients with other arthritides. The number of PB CD8- T cells expressing IFN-g after mitogen stimulation was higher in controls than in patients. In PB monocytes the ratio of CCR5+/CCR3+ cells was increased in patients with RA compared to patients with other arthritides and controls.


CONCLUSIONS
T cells and monocytes infiltrating joints in RA and in other arthritides showed increased activation of both type 1 and type 2 immune markers. More pronounced type 1 immune response in joints, shown as an increased CCR5/CCR3 ratio, was found in the patients with RA versus those with other arthritides. Monocytes but not T cells in PB showed increased activation in RA.
Nissinen
Riikka
R
Department of Molecular Medicine, National Public Health Institute, Biomedicum, PO Box 104, 00251 Helsinki, Finland. riikka.nissinen@ktl.fi
Leirisalo-Repo
Marjatta
M
Tiittanen
Minna
M
Julkunen
Heikki
H
Hirvonen
Hanna
H
Palosuo
Timo
T
Vaarala
Outi
O
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis*; D015847:Interleukin-4 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D011336:Probability; D019713:Receptors, CCR5 / Q000032:analysis / Q000378:metabolism; D018121:Receptors, Cytokine / Q000032:analysis / Q000378:metabolism*; D012494:Sampling Studies; D018709:Statistics, Nonparametric; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D015415:Biomarkers; D019713:Receptors, CCR5; D018121:Receptors, Cytokine; D015847:Interleukin-4; D007371:Interferon-gamma