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

Decreased Accumulation of DCs in the T Cell Zones of plt Mice. plt mice have a defect in the homing of naive T cells that leads to a marked decrease in the number of these cells in the T cell zones of LNs, PPs, and spleen. The finding that SLC is not expressed in plt mice strongly supports the hypothesis that SLC is required for naive T cell homing. Like naive T cells, activated DCs migrate to the T cell zones of secondary lymphoid organs. Therefore, we examined the distribution of DCs in plt mice. By FACS ® analysis, DC numbers were decreased 60% in the LNs of plt mice (Fig. 2 A) . The average number of total I-A ϩ DCs in the pooled LNs of ϩ/ϩ mice was 24.5 Ϯ 4.7 ϫ 10 3 per mouse compared with 9.1 Ϯ 2.4 ϫ 10 3 in plt mice (P Ͻ 0.01, n ϭ 3). Immunohistochemistry established that this decrease was most pronounced in the deep cortex. Those DCs that were present in plt mice typically clustered in the internodular cortex (Fig. 3, A and B ). In the spleens of plt mice, the total number of DCs was normal (Fig. 2 B) , but there was a striking abnormality in cell distribution (Fig. 3) . Staining with anti-CD11c revealed a marked decrease in the number of DCs within the white pulp (Fig. 3 , C and D). There was a concomitant increase in the number of DCs located outside the white pulp, either in bridging channels or in isolated clusters within the red pulp, such that the total number of splenic DCs remained normal. Staining with NLDC-145, which in the spleen is specific for interdigitating DCs (34) , also revealed a decrease in the number of these cells within the white pulp and demonstrated that those DCs outside the white pulp were NLDC-145 negative (Fig. 3, E and F) .