Migration of CX3CR1‐positive T cells producing type 1 cytokines and cytotoxic molecules into the synovium of patients with rheumatoid arthritis

Abstract

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-␥ and tumor necrosis factor ␣, 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.Conclusion. 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.

Coronary Spastic Angina in Patients With Connective Tissue Disease

“…The peripheral CD4 + and CD8 + T cells expressing CX3CR1 predominantly produced IFN-and tumor necrosis factor . 19 Those data are compatible with our result that the frequency of IFN--producing T cells was significantly higher in the connective tissue disease group than in normal subjects. We have recently reported a significant increase in activated T cells in patients with not only unstable angina but also coronary spastic angina.…”

IFN-γ Alters the Response ofBorrelia burgdorferi-Activated Endothelium to Favor Chronic Inflammation

“…However, IL-1␤ and TNF-␣ are secreted by human monocytes in response to B. burgdorferi (50), which suggests that these cytokines may potentiate the effects of IFN-␥ on synthesis of chemokines in LD. In addition, other inflammatory arthritides, such as rheumatoid and septic arthritis, are characterized by marked increases in the levels of many of the chemokines that are synergistically up-regulated by B. burgdorferi and IFN-␥, including CCL8, CXCL9, CXCL10, CXCL11, and CX3CL1 (48,49,(51)(52)(53)(54). IFN-␥ thus cooperates with several proinflammatory stimuli to enhance secretion of chemokines and thereby likely facilitates enhanced recruitment of leukocytes and ongoing inflammation in a variety of pathological conditions.…”

Chemokines and their receptors in rheumatoid arthritis: Future targets?

“…In RA ST, macrophages and dendritic cells were the predominant cells bearing CX 3 CR1 (81). CX 3 CR1 has been implicated in both monocyte recruitment and lymphocyte recruitment in the RA joint (81,93).…”