Cell contact-mediated signaling of monocytes by stimulated T cells: a major pathway for cytokine induction

T lymphocytes are currently thought to play a pivotal part in the pathogene sis of chronic inflammatory diseases. However, the mechanism(s) by which th ey exert their pathogenic effect remain(s) elusive. Contact-mediated signal ing of monocytes by stimulated T cells is a potent pro-inflammatory mechani sm that triggers massive up-regulation of the pro-inflammatory cytokines in terleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) that play an important part in chronic destructive diseases such as rheumatoid arthriti s and multiple sclerosis. To date cell-cell contact is the only endogenous mechanism to be described that displays such an activity in monocyte-macrop hages which are classically stimulated in vitro by bacterial products such as LPS or non-specific stimuli such as phorbol esters or poorly activated b y soluble cytokines such as IFN-gamma. Since direct cellular contact occurs at the inflammatory site, we hypothesized that this mechanism is relevant to the pathogenesis of chronic inflammatory disorders. This review aims at summarizing the state of the art and importance of contact-mediated monocyt e activation by stimulated T lymphocytes.