Co‐stimulatory and adhesion molecules of dendritic cells in rheumatoid arthritis

Abstract

Dendritic cells (DCs) in the rheumatoid arthritis (RA) joint mediate the immunopathological process and act as a potent antigen presenting cell. We compared the expression of co‐stimulatory and adhesion molecules on DCs in RA patients versus controls with traumatic joint lesions and evalulated the correlation between the immunophenotypical presentation of DCs and the clinical status of the disease. Samples of peripheral venous blood, synovial fluid (SF) and synovial tissue (ST) were obtained from 10 patients with RA at the time of hip or knee replacement and from 9 control patients with knee arthroscopy for traumatic lesions. Clinical status was appreciated using the DAS28 score. Blood, SF and dissociated ST cell populations were separated by centrifugation and analyzed by flow cytometry. Cells phenotypes were identified using three‐color flow cytometry analysis for the following receptors HLA‐DR, CD80, CD83, CD86, CD11c, CD18, CD54, CD58, CD3, CD4, CD8, CD19, CD20, CD14, CD16, CD56. HLA‐DR molecules, co‐stimulatory receptors CD80, CD86, CD83 and adhesion molecules CD18, CD11c, CD54, CD58, were analyzed by two‐color immunofluorescence microscopy on ST serial sections. In patients with active RA (DAS28>5.1) we found a highly differentiated subpopulation of DCs in the ST and SF that expressed an activated phenotype (HLA‐DR, CD86+, CD80+, CD83+, CD11c+, CD54+, CD58+). No differences were found between circulating DCs from RA patients and control patients. Our data suggest an interrelationship between clinical outcome and the immunophenotypical presentation of DCs. Clinical active RA (DAS28>5.1) is associated with high incidence of activated DCs population in the ST and SF as demonstrated by expression of adhesion and co‐stimulatory molecules.

Oral bacteria induce a differential activation of human immunodeficiency virus‐1 promoter in T cells, macrophages and dendritic cells

“…Stained cells were washed twice with PBS/bovine serum albumin and analysed using an EPICS XL flow cytometer and expo 32 software (Beckman Coulter, Fullerton, CA). Compared with the THP‐1 cells, the iDC and mDC have differential expression of CD80, CD83, CD86 and HLA‐DR, with iDC being CD80 hi , CD83 lo , CD86 lo , HLA‐DR lo , and mDCs phenotypically described by CD80 hi , CD83 hi , CD86 hi , HLA‐DR hi compared with the original THP‐1 cells (4, 22, 32).…”

Recruitment of dendritic cells and macrophages during T cell-mediated synovial inflammation

“…In an autoimmune disease such as rheumatoid arthritis, the presence of large numbers of activated DCs in the affected synovium [ 12 , 13 ] suggests that these cells present local autoantigens to cognate effector T cells in situ [ 14 , 15 ]. However, studies on pathological specimens present a static picture, usually of established disease, and there is little information available about the kinetics of recruitment of DC precursors in the early rheumatoid lesion.…”

Constrained Cyclic Peptides as Immunomodulatory Inhibitors of the CD2:CD58 Protein–Protein Interaction

“…3,4 The interaction between CD2 and CD58 has significant importance in autoimmune diseases such as rheumatoid arthritis (RA). 5–7 The results of large genome-wide association studies (GWAS) suggest that more than 30 loci are involved in RA pathogenesis, and CD2 as well as CD58 is important. 6 Previous reports have indicated that inhibition of the CD2 and CD58 interactions using a LFA-3 fusion protein (alefacept) inhibits T-cell activation.…”