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

The involvement of SLC in naive lymphocyte homing was initially suggested by its expression on HEVs (23) . Similarly, the expression of SLC at sites such as lymphatic endothelium suggested to us that SLC may be involved in other leukocyte trafficking events and that plt mice may have other leukocyte trafficking defects. We now find that plt mice have a defect in the migration of DCs into the T cell zones of lymphoid organs. Four lines of evidence support this finding. First, the number of DCs in the T cell zones of LNs and spleen in plt mice is decreased (Fig. 3) . In the spleen, this decrease occurs despite a normal total number of splenic DCs (Fig. 2) . Second, DCs appear to accumulate at the periphery of T cell zones in both LNs and spleen of plt mice (Fig. 3) . The pattern of this accumulation is consistent with a block in the entry of DCs into T cell zones. Third, we directly demonstrate a decrease in the migration of FITC-activated DCs to draining LNs of plt mice (Fig. 4) . It is possible that this defect in DC migration is secondary to the paucity of T cells in the LNs of plt mice. However, in both L-selectin knockout mice, which have a defect in the homing of naive lymphocytes to LNs similar to that of plt mice, and nude mice, which lack mature T cells, FITC-stimulated migration of DCs to LNs is normal (12, 35, 45, 46) . This suggests that DC migration to LNs is not lymphocyte dependent. Fourth, splenic DCs in the bridging channels and red pulp of plt mice fail to redistribute to the T cell zone upon activation with LPS (Fig. 5, C and D) . Taken together, these results suggest that plt mice lack a factor that acts directly on DCs to stimulate their migration. Due to its lack of expression, the probable identity of this factor is SLC.