EXPRESSION AND FUNCTION OF CD80 AND CD86 COSTIMULATOR MOLECULES ON SYNOVIAL DENDRITIC CELLS IN CHRONIC ARTHRITIS

Objective, To examine CD86 expression on dendritic cells isolated from the synovial fluid (SFDC) of patients with chronic arthritis, and to determine the importance of both CD80 and CD86 molecules in SFDC-T lym phocyte interactions, Methods, CD86 messenger RNA (mRNA) and surface e xpression were analyzed in SFDC using reverse transcriptase-polymerase chain reaction and flow cytometry, respectively, The costimulator act ivity of the SFDC CD80 and CD86 molecules was determined by allogeneic mixed lymphocyte reaction (MLR), CD80 and CD86 induction on SFDC duri ng in vitro culture was also examined, Results, Fresh SFDC either lack ed or showed very weak surface expression of CD86 molecules (as shown previously for CD80), yet contained CD86 mRNA, CD80 antibodies minimal ly inhibited an allogeneic MLR, whereas CD86 antibodies and CTLA-4 Ig showed significant inhibition, Both CD80 and CD86 molecules were incon sistently induced on SFDC following culture in either media, interfero n-gamma, or granulocyte-macrophage colony-stimulating factor, Conclusi on, SFDC may be defective antigen-presenting cells in vivo. The abilit y of CD80 and CD86 molecules to be induced and become functional on SF DC in vitro implies the presence of a negative regulatory compound(s) in the synovial environment.