Mice Lacking Expression of the Chemokines Ccl21-Ser and Ccl19 (plt Mice) Demonstrate Delayed but Enhanced T Cell Immune Responses

Abstract

The paucity of lymph node T cells (plt) mutation leads to a loss of CCL21 and CCL19 expression in secondary lymphoid organs. plt mice have defects in the migration of naive T cells and activated dendritic cells into the T cell zones of lymphoid organs, suggesting that they would have defects in T cell immune responses. We now demonstrate T cell responses in plt mice are delayed but ultimately enhanced. Responses to contact sensitization are decreased at day 2 after priming but increased at day 6. After subcutaneous immunization, antigen-specific T cell proliferation and cytokine production in plt mice are increased and remain markedly elevated for at least 8 wk. Compared with wild-type mice, a proportion of T cell response in plt mice are shifted to the spleen, and prior splenectomy reduces the T cell response in draining lymph nodes. After immunization of plt mice, T cells and dendritic cells colocalize in the superficial cortex of lymph nodes and in splenic bridging channels, but not in T cell zones. These results demonstrate that plt mice mount robust T cell responses despite the failure of naive T cells and activated dendritic cells to enter the thymus dependent areas of secondary lymphoid organs.

Fibroblastic reticular cells of the lymph node are required for retention of resting but not activated CD8 + T cells

“…Previous studies have shown that mice lacking CCL19/21 (paucity of lymph node T cells or plt) display delayed but enhanced immune responses (7,33,34). Whereas there is an altered pro-Th1-type inflammatory infiltrate in immunized plt LNs (34), other studies suggest that T-cell responses in these mice may be generated in the splenic red pulp or the cortex of the LN (7), potentially contributing to the enhanced responses observed.…”

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

“…Lymph node development and organization is accomplished mainly by the differential expression of CCL21 and CXCL13 in the T and B cell zones, respectively [62][63][64][65]. CCL21 and CXCL13 are ligands for CCR7 and CXCR5 (expressed by B cells), respectively, and are secreted by mesenchymal cells in the early developing lymph node to drive lymphoid tissue formation through the attraction of CD3ε − CD4 + IL-7Rα hi CCR7 + and CXCR5 + lymphoid tissue inducer cells [62,66].…”

Visualizing dendritic cell migration within the skin

“…CCL19 is primarily expressed by LN Wbroblastic reticular cells (Chen et al 2002;Vassileva et al 1999;Weninger and von Andrian 2003). In mice that have a naturally occurring deletion of CCL21-Ser and CCL19 (paucity of lymph node T cells, plt/plt), DCs are capable of entering lymphatics in the skin, but accumulate in the superWcial cortex of draining LNs (Mori et al 2001).…”