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

Chemokines are implicated in two distinct steps in lymphocyte extravasation. First, they can stimulate integrin activation and the firm adhesion of rolling lymphocytes. Second, they can provide a chemotactic signal for lymphocyte migration through the endothelium and into the underlying tissue. We believe that SLC is the chemokine that mediates the first of these steps during the homing of naive T cells to LNs and PPs. Evidence in support of this conclusion includes the expression of SLC on HEVs, the ability of SLC to activate both ␣ L ␤ 2 and ␣ 4 ␤ 7 integrins on T cells, the ability of SLC to stimulate the rapid arrest of rolling T cells with an efficiency similar to that seen in vivo, and the absence of any other known chemokine with similar characteristics. We now add to this body of evidence by demonstrating that mice homozygous for the plt mutation do not express SLC (Fig. 1) . The lymphocyte homing defect in plt mice is similar to that seen when naive T cells are treated with pertussis toxin-failure of naive T cells to enter LNs, PPs, or the white pulp of spleen, suggesting that the defect in plt mice occurs in the initial steps of lympho-cyte extravasation (29, 42, 43) . Like pertussis toxin treatment, the lymphocyte homing defect in plt mice probably represents a loss of the signal for the integrin-mediated firm adhesion of naive T cells.