The Role Of Initiation And Ligand Interaction Of Resting...

2.2.3 Role of VLA-4 in Costimulation Integrin receptor/ligand interactions provide a potent costimulatory signal to CD3-mediated T cell activation (Davis et al., 1990; Nguyen et al., 2008). Specifically, the VLA-4 mediated interaction of resting human CD4+ T lymphocytes with FN has been shown to promote CD3-mediated T cell proliferation (Shimizu et al., 1990). Coimmobilization with mAb to CD3 and FN consistently resulted in strong T cell proliferation. Other investigators showed that immobilized FN enhances anti-CD3 induced proliferation of both CD45RAdim (memory) and CD45RAHI (naà ¯ve) subsets of CD4+ and CD8+ T cells, and that this effect was inhibited with a mAb against the ÃŽ ²1 subunit of VLA-4. Additionally, Nojima et al. showed that the A and B epitopes of VLA-4 play a key role in VLA-4 mediated T cell costimulation (Nojima et al., 1990). 2.3 Role of ÃŽ ±4-integrin in CNS immunocompetence 2.3.3 ÃŽ ±4-integrin Antagonism in EAE As previously described, leukocytes activated in the periphery are able to adhere to the endothelium of blood vessel walls in order to traffic into the CNS, where re-activation by antigen presentation from perivascular APC leads to inflammation. In 1992, Yednock et al., which would later develop a successful therapy for RRMS patients, made a revolutionary finding. They reported that lymphocytes and monocytes bound selectively to inflamed EAE brain vessels and that this could be reversed with antibodies against VLA-4 (Yednock et al., 1992). When tested inShow MoreRelatedInnate Immunity : An Early Phase Of Defence Mechanism Against Intruding Microorganisms5373 Words   |  22 Pagesprovides an early phase of defence mechanism against intruding microorganisms, mediated by phagocytes such as macrophages and dendritic cells (DCs), having the ability to distinguish between self and non-self (pathogens). The innate immune system recognises microorganisms by germ-line encoded pattern recogn ition receptors (PRRs), expressed on all types of cells. The metabolic products generated by microbial pathogens rather than the host allow the immune system to differentiate between the self and