Immunomodulation by monoclonal antibodies directed against cell adhesion molecules: A special case for CD4 monoclonal antibodies

The induction as well as the effector phase of cellular immune reactions depend on specific cell-cell contacts. Besides the specific antigen receptors, adhesion molecules on the cell surface play a pivotal role in the guidance and stabilisation of temporary contacts required for inter- and intracellular signal transduction. Of the various adhesion molecules, such as ICAM-1, CD2, LFA-1 and LFA-3, the CD4 and CD8 glycoproteins play a particular role because they direct T-cell subsets specifically to either major histocompatibility complex (MHC) class II or MHC class I molecules which are associated with the triggering antigen on antigen-presenting cells. The blockade of both adhesion molecules by antibodies efficiently inhibits the function of the respective T-cell subsets. One of the most efficient ways to suppress T-cells in experimental autoimmune disorders has been the therapeutic administration of CD4 monoclonal antibodies. Studies have therefore concentrated on the immunomodulation induced by CD4 monoclonal antibodies in patients with rejection crises of organ transplants and patients with rheumatoid arthritis.