The chemokines CCL5, CCL2 and CXCL12 play significant roles in the migration of Th1 cells into rheumatoid synovial tissue.
As the T-cell population in the synovial tissue (ST) in rheumatoid arthritis (RA) is dominated by T helper (Th) 1 cells, this study was designed to examine whether there is a preferential migration of polarized T cells to ST, and to identify the chemokines responsible for the migration. This was done by developing 10 T-cell clones specific for an arbitrary antigen (mouse immunoglobulin G (IgG)) from the peripheral blood (PB) of a healthy donor sensitized to mouse IgG. The Th polarizations of the clones were determined by measuring secreted interferon-gamma and interleukin-4, following anti-CD3 stimulation. Migration to pools of RA ST cell-derived supernatants was analysed. Expression of the chemokine receptors CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CXCR3 and CXCR4 were analysed by flow cytometry. Th1 clones showed significantly higher migration to RA ST cell-derived supernatant compared with Th2 clones. Blocking of either of the chemokines, CCL5 or CCL2, strongly inhibited migration of the Th1 cells between 56 and 77%, while blocking of CXCL12 inhibited migration between 44 and 61%. Blocking of CXCL10 had only a minor inhibitory effect. Our results demonstrate a selective migration of Th1 cells to RA ST supernatant and that blocking either CCL5, CCL2 or CXCL12 significantly inhibits T-cell migration. This indicates that CCL5, CCL2 and CXCL12 play significant roles in attracting Th1 cells towards the RA ST, and may prove potent targets for obstructing T-cell migration to the synovium.
Shadidi
K R
KR
Rikshospitalet University Hospital, Institute of Immunology, Section of Rheumatology Research, Oslo, Norway.
Aarvak
T
T
Henriksen
J E
JE
Natvig
J B
JB
Thompson
K M
KM
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D018925:Chemokines / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019707:Receptors, Chemokine / Q000276:immunology; D018709:Statistics, Nonparametric; D013583:Synovial Membrane / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D017252:CD3 Complex; D018925:Chemokines; D007074:Immunoglobulin G; D019707:Receptors, Chemokine