Stromal cell derived factor-1 (CXCL12) induces cell migration into lymph nodes transplanted into SCID MICE. An investigation of lymphocyte migration to secondary lymphoid organs

SDF-1 (CXCL12), a CXC chemokine, has a primary role in signalling the recruitment of haematopoietic stem-cell precursors to the bone marrow during embryonic development. In post-natal life, SDF-1 is widely expressed and is induced in chronically inflamed tissues such as psoriatic skin and the rheumatoid synovium, but has also been implicated in the migration of lymphocytes to lymphoid organs. To investigate the role of SDF-1 in recirculation and homing in vivo we have developed a model in which human peripheral lymph nodes (huPLN) are transplanted into SCID mice. We have shown that huPLN transplants are viable and are vascularised by the murine circulation, forming functional anastomoses with transplant vessels. In addition grafts retain some of the histological features of the pretransplantation tissue, such as follicular dendritic cell-associated B-cell aggregates, lymphatic and HEV markers. We also show that SDF-1 is capable of inducing the migration of an SDF-1 responsive cell-line (U-937) and human PBL's from the murine circulation into the grafts in a dose dependant manner which is inhibitable by CXCR4 blockade. The mechanism of action of SDF-1 in this model is independent from that of TNF-α and does not rely on the upregulation of adhesion molecules (such as ICAM-1) on the graft vascular endothelium. This is the first description of huPLN transplantation into SCID mice, and of the functional effects of SDF-1 regarding the migration of human cells into huPLN in vivo. This model provides a powerful tool to investigate the pathways involved in cell-migration into lymphoid organs and potentially to target them for therapeutic purposes.