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

Arthritis Rheum. 2002 Nov;46(11):2878-83. doi: 10.1002/art.10622.


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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / metabolism*
  • CD4-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / chemistry
  • Cell Movement / physiology*
  • Chemokines, CX3C / analysis*
  • Chemokines, CX3C / blood
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Receptors, Interleukin-8A / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synovial Membrane / chemistry
  • Synovial Membrane / cytology
  • T-Lymphocytes / chemistry*
  • T-Lymphocytes / immunology


  • Chemokines, CX3C
  • Receptors, Interleukin-8A