Mice Lacking Expression of Secondary Lymphoid Organ Chemokine Have Defects in Lymphocyte Homing and Dendritic Cell Localization

Gunn, Michael D.; Kyuwa, Shigeru; Tam, Carmen; Kakiuchi, Terutaka; Matsuzawa, Akio; Williams, Lewis T.; Nakano, Hideki

SLC (also known as 6Ckine, Exodus-2, and TCA4 [19] [20] [21] [22] ) is a recently identified chemokine that is expressed in the HEVs of LNs and PPs, in nondendritic stromal cells within the T cell areas of LNs, spleen, and PPs, in the thymic medulla, and in the lymphatic endothelium of multiple tissues (22, 23) . SLC has been hypothesized to mediate the homing of naive lymphocytes to secondary lymphoid tissues based on several findings (23) . SLC is the only chemokine known to be constitutively expressed in the endothelial cells of HEVs (23) . SLC stimulates the chemotaxis of naive T cells and, to a lesser extent, memory T cells and B cells (23, 24) . SLC stimulates both the ␣ L ␤ 2 integrinmediated adhesion of T cells to intercellular adhesion molecule (ICAM)-1 and the ␣ 4 ␤ 7 integrin-mediated adhesion of these cells to mucosal addressin cell adhesion molecule (MadCAM)-1 (23, 25, 26) . Activated ␣ L ␤ 2 function is essential for lymphocyte homing to LNs and PPs, and activated ␣ 4 ␤ 7 is required for homing to PPs. Under physiologic flow conditions, SLC stimulates the arrest of rolling T cells with an efficiency and subset specificity (naive versus memory) similar to that seen in vivo (27) . These properties strongly suggest that SLC mediates the homing of naive T cells and perhaps other lymphocytes to secondary lymphoid organs; however, this has not been demonstrated directly.