Regulation of CCR5 expression and MIP-1alpha production in CD4+ T cells from patients with rheumatoid arthritis

Clin Exp Immunol. 2003 May;132(2):371-8. doi: 10.1046/j.1365-2249.2003.02126.x.

Abstract

Production of CCR5 expression and MIP-1alpha, a ligand of CCR5, by CD4+ T cells from patients with rheumatoid arthritis (RA) were studied. We analysed further the influence of IL-15 stimulation, CD40/CD40 ligand (CD40L) interaction and CCR5 promotor polymorphism. One hundred and fifty-five RA patients and another 155 age- and sex-matched healthy individuals were enrolled. Peripheral CD4+ and double negative (DN) T cells from patients had lower portions of CCR5, whereas synovial CD4+ and DN T cells showed a much higher CCR5 expression. IL-15 significantly up-regulated the expression of CCR5 on purified CD4+ T cells. CD40L expression on synovial CD4+ T cells was increased greatly in CCR5+ portions by IL-15. MIP-1alpha production by synovial CD4+ T cells was also enhanced by IL-15. Co-culture of CD40 expressing synovial fibroblasts with IL-15-activated synovial CD4+ T cells significantly increased MIP-1alpha production. Expression of CCR5 on patients' CD4+ T cells was not influenced by the promotor polymorphism of CCR5 gene. Taken together, these data suggest CCR5+CD4+ T cells infiltrate the inflamed synovium and IL-15 up-regulates CCR5 and CD40L expression further and enhance MIP-1alpha production in synovial CD4+ T cells. Production of MIP-1alpha by synovial fibroblasts is significantly increased by engagement of CD40 with CD40L. Synovial microenvironment plays a potential role in regulation of CCR5+CD4+ T cells in rheumatoid joints.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD40 Antigens / metabolism
  • CD40 Ligand / metabolism
  • Case-Control Studies
  • Cells, Cultured
  • Chemokine CCL3
  • Chemokine CCL4
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Genotype
  • Humans
  • Interleukin-15 / pharmacology
  • Macrophage Inflammatory Proteins / biosynthesis*
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length
  • Protein Isoforms / analysis
  • Protein Isoforms / biosynthesis
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism*
  • Statistics, Nonparametric
  • Synovial Membrane / immunology*

Substances

  • CD40 Antigens
  • Chemokine CCL3
  • Chemokine CCL4
  • Interleukin-15
  • Macrophage Inflammatory Proteins
  • Protein Isoforms
  • Receptors, CCR5
  • CD40 Ligand