Regulation of CCR5 expression and MIP-1alpha production in CD4+ T cells from patients with rheumatoid arthritis.
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.
Wang
C R
CR
Section of Rheumatology, Department of Internal Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan. wangcr@mail.ncku.edu.tw
Liu
M F
MF
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005838:Genotype; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020033:Protein Isoforms / Q000032:analysis / Q000096:biosynthesis; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013583:Synovial Membrane / Q000276:immunology*
D019013:CD40 Antigens; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019409:Interleukin-15; D019402:Macrophage Inflammatory Proteins; D020033:Protein Isoforms; D019713:Receptors, CCR5; D023201:CD40 Ligand