Cell-cell interactions in synovitis: antigen presenting cells and T cell interaction in rheumatoid arthritis

Abstract

The synovial tissue in rheumatoid arthritis (RA) patients is enriched with mature antigen presenting cells (APCs) and many T lymphocytes. Interactions between APCs and T cells are essential for the initiation and amplification of T-cell-dependent immune responses, and may therefore play an important role in the chronic inflammatory processes in the synovium. The nature of the antigen(s) involved in RA still remains elusive. However, interactions and signaling through the costimulatory molecules CD28-CD80/86 and CD40-CD40L are critical during APC-T cell interaction for optimal cell activation. This review discusses how such costimulatory signals can be involved in the initiation and amplification of the inflammatory reactions in the synovium. Blocking of the signaling pathways involved in APC-T cell interactions might provide a specific immuno-therapeutic approach for the treatment of RA.

Figure 1

Antigen presenting cell-T cell interaction in the synovium. Dendritic cells (DCs) in the synovium present an external or local antigen to T cells. T cell receptor interaction and signaling via CD28-CD80/86 are essential for initial T cell activation leading to upregulation of CD40L on the T cells. Activated T cells are then capable of inducing further differentiation of DCs, as well as T cell help to rheumatoid factor B cells that have taken up antigen-Ig complexes. CD40-CD40L interaction between DCs, B cells and T cells may play a critical role in repeated activation of memory T cells in the synovium and, thus, maintenance of the inflammatory reactions.