Evidence in support of a self-perpetuating HLA-DR-dependent delayed-type cell reaction in rheumatoid arthritis

Abstract

Originating from observations on similarities between the rheumatoid synovial tissue and skin lesions in delayed-type hypersensitivity reactions--similarities as to massive infiltrates of "helper" T lymphocytes close to HLA-DR-expressing macrophage/dendritic cells--a notion is formed on the importance of local macrophage-dependent helper T-cell activation in the rheumatoid joint similar to that in a delayed-type skin reaction. In vitro studies on suspended synovial cells have been used to test and qualify these ideas. It is shown that (i) HLA-DR-expressing cells in normal synovial intima can, like epidermal Langerhans cells, mediate T-cell activation; (ii) the large numbers of rheumatoid synovial HLA-DR-expressing macrophage-like/dendritic cells are heterogeneous and mediate either efficient activation or suppression of T-lymphocyte proliferation, and (iii) specificity of rheumatoid T cells can be analyzed with the help of autologous synovial antigen-presenting cells; a specific anti-collagen type II response is reported in three patients.