Location, location, location is not just something considered by concerned house buyers, but is also important for cells of the immune system to ensure that effective immune responses are mounted. Lymphocytes must be in the right place for both their activation and to mediate their effector functions. Two articles this month focus on the mechanisms involved in getting lymphocytes to the right location. On page 360, Masayuki Miyasaka and Toshiyuki Tanaka discuss the recruitment of naive lymphocytes into lymphoid organs from specialized postcapillary venules and highlight an important role for immobilized chemokines in this process. After activation, T cells are then required to enter extralymphoid tissues and sites of inflammation. The role of selectins and their glycoprotein ligands in the trafficking of T cells to non-lymphoid tissues is reviewed by Klaus Ley and Geoffrey Kansas on page 325.
Once on site, signals mediated through cell-surface molecules and intracellular signalling proteins converge to bring about the appropriate immune response. On page 336, Lieping Chen describes the fine balance of positive and negative signals mediated through the B7–CD28 family of co-inhibitory molecules that modulate responses to T-cell receptor ligation. And Margot Thome outlines the exciting new studies that identify key intracellular signalling components — CARMA1, BCL-10 and MALT1 — involved in connecting antigen-receptor triggering with lymphocyte activation through the nuclear factor-κB pathway.
