Regulation of CCR5 expression and MIP-1α 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.