Synovial fluid mononuclear cells exhibit a spontaneous HLA-DR driven proliferative response.

We have tested the hypothesis that the spontaneous proliferation of synovial fluid mononuclear cells (SFMC) observed during in vitro culture is due to a mechanism analogous to the autologous mixed lymphocyte reaction (AMLR). Thus by observing the effect of addition of cyclosporin A, monoclonal anti-HLA-DR antibody, and recombinant interleukin 2 (rIL-2) on the spontaneous proliferation of SFMC from patients with rheumatoid arthritis (RA) and a wide range of seronegative spondyloarthritides (SN), we have demonstrated that this phenomenon is: (i) a T cell response, (ii) inhibited by the addition of cyclosporin A or monoclonal anti-HLA-DR antibody, (iii) enhanced by the addition of rIL-2 and (iv) the rIL-2 enhancement of the spontaneous proliferation is inhibited by a monoclonal anti-HLA-DR antibody. These observations suggest that the spontaneous proliferation of SFMC is at least in part an HLA-DR driven, IL-2 dependent event analogous to the AMLR, and support the concept derived from immunohistological studies of an important role for an antigen-presenting cell/T cell interaction occurring in the synovial membrane in inflammatory joint diseases such as RA.