Selective recruitment of CXCR3+ and CCR5+ CCR4+ T cells into synovial tissue in patients with rheumatoid arthritis

Acta Med Okayama. 2006 Jun;60(3):149-57. doi: 10.18926/AMO/30745.

Abstract

The inflamed synovial tissue (ST) of rheumatoid arthritis (RA) is characterized by the selective accumulation of interferon gamma-producing Th1-type CD4+ T cells. In this study, we investigated whether the predominance of Th1-type CD4+ cells in the ST lesion is mediated by their selective recruitment through Th1 cell-associated chemokine receptors CXCR3 and CCR5. The lymphocyte aggregates in the ST of RA contained a large number of CD4+ T cells, which mostly expressed both CXCR3 and CCR5, but not CCR4. In contrast, the frequencies of CD4+ and CD8+ T cells expressing CXCR3 and CCR5 in the blood were significantly decreased in RA patients, compared with healthy controls (HC), although there was no difference in the frequencies of CCR4-expressing CD4+ and CD8+ T cells between RA and HC. CXCR3, CCR5, and CCR4 expression in blood CD4 + T cells and CXCR3 expression in CD8+ T cells were increased after interleukin-15 (IL-15) stimulation. Therefore, the distribution of Th1-type CD4+ T cells into the ST from the blood in RA may be associated with the local expression of chemokines, both CXCR3 and CCR5 ligands, and IL-15 may play a role in enhancing these chemokine receptors on CD4+ T cell infiltrates.

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / physiopathology*
  • CD4-Positive T-Lymphocytes / chemistry*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology*
  • CD8-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / pathology
  • Case-Control Studies
  • Cell Movement / physiology
  • Female
  • Flow Cytometry
  • Humans
  • Interleukin-15 / physiology
  • Ligands
  • Male
  • Middle Aged
  • Receptors, CCR4
  • Receptors, CCR5 / metabolism*
  • Receptors, CXCR3
  • Receptors, Chemokine / analysis
  • Receptors, Chemokine / metabolism*
  • Synovial Membrane / immunology*
  • Synovial Membrane / physiopathology
  • Th1 Cells / immunology
  • Th1 Cells / pathology

Substances

  • CCR4 protein, human
  • CXCR3 protein, human
  • Interleukin-15
  • Ligands
  • Receptors, CCR4
  • Receptors, CCR5
  • Receptors, CXCR3
  • Receptors, Chemokine