Chemokines and the Homing of Dendritic Cells to the T Cell Areas of Lymphoid Organs

A quarter of a century ago, it was proposed that veiled cells in the lymph were antigen-bearing Langerhans' cells (LCs) en route to the LN T cell area (1, 2). Extensive investigations have since established that LCs are immature dendritic cells (DCs) and that insults to the skin—including exposure to contact sensitizers, bacteria, or UV light— cause many of these cells to enter lymphatic vessels and travel to LNs (3). During transit the cells undergo a program of maturation events that take them from being poorly immunogenic to being the most potent of all APCs (3). Rapid transit of maturing DCs from the site of infection to the draining lymphoid tissue is likely to be critical for quick initiation of the adaptive immune response. But how do these cells migrate to lymphatics and subsequently into the LN T zone? A flurry of recent studies (4–9) have implicated chemokines and chemokine receptors in directing DC migration, and now a study reported in this issue provides strong evidence that one chemokine, secondary lymphoid tissue chemokine (SLC), plays an important role in DC migration in vivo to T cell zones of LNs and spleen (10). Chemokines are small basic proteins that engage seven transmembrane receptors on responsive cells and promote chemotaxis (11). First characterized for their role in attracting cells to sites of inflammation, chemokines have more recently been found to direct cell movements within lym-phoid tissues. Two chemokines that have been suggested to serve a homing function in the T cell compartment are SLC/6Ckine (12–16) and EBV-induced molecule 1 ligand chemokine (ELC)/macrophage inflammatory protein (MIP)-3 ␤ (17–19). SLC and ELC are structurally related chemokines and both bind the receptor CCR7 (20, 21). SLC is expressed at high levels by high endothelial venules (HEVs) in LNs and at lower levels by a poorly defined population of stromal cells in T cell areas of LNs, spleen, and Peyer's patches (13, 15, 16). ELC is made by a subset of DCs, and possibly by other nonlymphoid cells, in T cell areas of lymphoid tissue (19). Both chemokines are efficacious attractants of T lymphocytes (19, 21) and both can promote integrin activation on rolling lymphocytes (13, 22). Together these findings have led to the notion that SLC functions in recruitment of T cells across HEVs into LNs and more generally in promoting T cell migration into lymphoid T zones. ELC may work with SLC in recruiting …