Stromal Cell-Derived Factor 1 (CXCL12) Induces Human Cell Migration into Human Lymph Nodes Transplanted into SCID Mice

Stromal cell-derived factor 1 (SDF-1; CXCL12), a CXC chemokine, has a primary role in signaling the recruitment of hemopoietic stem cell precursors to the bone marrow during embryonic development. In postnatal 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, vascularized by the murine circulation that forms functional anastomoses with transplant vessels. In addition, grafts retain some features of the pretransplantation tissue, such as lymphoid follicles, lymphatic and high endothelial venule markers. We also show that SDF-1 is capable of inducing the migration of a SDF-1-responsive cell line (U937) and human PBLs from the murine circulation into the grafts in a dose-dependent manner, inhibitable by CXCR4 blockade. The mechanism of action of SDF-1 in this model is independent from that of TNF-alpha and does not rely on the up-regulation 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 in regard to 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.