Active MAC-1 (CD11b/CD18) on DCs inhibits full T-cell activation

The beta(2) integrins are important for transenclothelial migration of leukocytes as well as for T-cell activation during antigen presentation. Despite abundant expression of beta 2 integrins on antigen-presenting cells (APCs), their functional relevance for antigen presentation is completely unclear. We show here that dendritic cells (DCs) from CD18-deficient mice, which lack all functional beta(2) integrins, have no defect in antigen presentation. Moreover, DCs from normal mice express inactive 02 integrins that do not become activated on contact with T cells, at least in vitro. Pharmacologic activation of beta(2) integrins on DCs results in a significant reduction of their T cell-activating capacity. This effect is mediated by Mac-1 (CD11b/CD18) on DCs because it could be reversed via blocking antibodies against CD18 and CD11b. Furthermore, the antigen-presenting capacity of macrophages, which express constitutively active beta(2) integrins, is significantly enhanced on Mac-1 blockade. We therefore conclude that active CD11b/CD18 (Mac-1) on APCs directly inhibits T-cell activation.