[Cell adhesion molecules on lymphocytes and their role on signal transduction]

It has been shown that cell adhesion molecules, which mediate lymphocyte adhesion have an ability to provide costimulation signals in the cells. One of the representative adhesion molecules on T lymphocytes, b1 integrin is comprised by several subunits sharing a common b1 subunits, CD29, which is defined by monoclonal anti-4B4 antibody. We have demonstrated that b1 integrins function as a cell surface receptor for extracellular matrix (ECM) protein, such as collagen and fibronectin. We also found that fibronectin, ligand of b1 integrin, synergized with anti-CD3 antibody to promote proliferation of CD4 T cell in a serum free culture system, and also induced an independent signal which would be distinct from the CD3/TcR-mediated signal pathway of activation through the induction of an AP-1 transcription factor. Recent studies revealed that there is an accumulation of CD4+CD29+ T cells, memory T cells as well as prominent increase of a variety of inflammatory cytokines in the synovial fluid of patients with rheumatoid arthritis (RA). This suggests that b1 integrins may play an important role for the inflammatory mechanism in RA. Regulation of signal transduction mediated by adhesion molecules on lymphocytes may be the possible effective way for controlling the pathological inflammatory process in RA.