Proliferative response of synovial fluid and peripheral blood mononuclear cells to arthritogenic and non-arthritogenic microbial antigens and to the 65-kDa mycobacterial heat-shock protein

Abstract

Cellular immune responses to microbial antigens have been implicated in the pathogenesis of some forms of arthritis including reactive arthritis, Reiter's syndrome, ankylosing spondylitis and rheumatoid arthritis. We investigated the proliferative T cell responses of paired peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MC) to so-called arthritogenic bacteria (Yersinia enterocolitica and Salmonella typhimurium), to control antigens, such as Candida albicans, mumps virus and purified protein derivative, to the recombinant mycobacterial 65-kDa heat-shock protein (hsp 65) and the mitogen phytohemagglutinin (PHA) in 16 patients with different inflammatory rheumatic diseases. The [3H]thymidine uptake of unstimulated cells (medium control) as well as the proliferative response to the different antigens tested was markedly increased in SFMC irrespective of the underlying rheumatic disease. In contrast, mitogenic stimulation was decreased in SFMC. The proliferative response to the hsp 65 correlated significantly with the responses to Yersinia, Salmonella and Candida. These results may reflect an enhanced function of SF antigen-presenting cells, different functional properties and subset distributions of PB and SF T cells with a preferential accumulation of helper-inducer/memory T cells or a maintenance of an ongoing immune response by T cells cross-recognizing self epitopes such as epitopes located on the hsp 65. Thus, care should be taken in the interpretation of SF T cell responses to microbial antigens as diagnostic tools in arthritis.