Migration of CX3CR1-positive T cells producing type 1 cytokines and cytotoxic molecules into the synovium of patients with rheumatoid arthritis.
OBJECTIVE
Rheumatoid arthritis (RA) is characterized by chronic inflammation of multiple joints. Large numbers of T cells, which produce type 1 cytokines, infiltrate into RA synovium. Chemokines and chemokine receptors are considered to contribute to the T cell infiltration. In this study, we examined the role of CX3CL1/fractalkine and its receptor CX3C chemokine receptor 1 (CX3CR1) in the T cell migration into RA synovium.


METHODS
Using flow cytometry, immunohistochemistry, and reverse transcription-polymerase chain reaction, we analyzed CX3CR1 expression by peripheral blood and synovial T cells, and CX3CL1 expression in synovium from patients with RA. Cytokine and cytotoxic molecule expression by CX3CR1-positive T cells was analyzed by flow cytometry.


RESULTS
CX3CR1 expression by peripheral CD4+ and CD8+ T cells was up-regulated in RA patients. The peripheral CD4+ and CD8+ T cells expressing CX3CR1 predominantly produced interferon-gamma and tumor necrosis factor alpha, and expressed cytotoxic molecules such as granzyme A and perforin. Furthermore, CX3CR1+,CD3+ T cells infiltrated into RA synovium. CX3CL1, the unique ligand of CX3CR1, was expressed by endothelial cells and synoviocytes in RA synovium, but not in osteoarthritis synovium.


CONCLUSIONS
Our findings suggest that the interactions of CX3CL1 and CX3CR1 might contribute to the accumulation of CX3CR1+ T cells expressing type 1 cytokines and possessing cytotoxic granules in RA synovium.
Nanki
Toshihiro
T
Department of Bioregulatory Medicine and Rheumatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. nanki.rheu@tmd.ac.jp
Imai
Toshio
T
Nagasaka
Kenji
K
Urasaki
Yasuyo
Y
Nonomura
Yoshinori
Y
Taniguchi
Ken
K
Hayashida
Kenji
K
Hasegawa
Jun
J
Yoshie
Osamu
O
Miyasaka
Nobuyuki
N
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry; D002465:Cell Movement / Q000502:physiology*; D020523:Chemokines, CX3C / Q000032:analysis* / Q000097:blood; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D023062:Receptors, Interleukin-8A / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000737:chemistry / Q000166:cytology; D013601:T-Lymphocytes / Q000737:chemistry* / Q000276:immunology
D020523:Chemokines, CX3C; D023062:Receptors, Interleukin-8A