Systemic immune modulation using chemokine receptor 7 expressing porcine Sertoli cells

Abstract

BACKGROUND: Sertoli cells (SC) are known to have active mechanism for evading humoral immune response and are known to have immune modulatory effects in the presence of other antigens. This has led us to hypothesize that systemic immune modulating effect of SC might be optimized by their residence on peripheral lymph node. This study was designed to evaluate our new strategy to promote preventive or therapeutic effects of SC in systemic immune modulation for organ transplantation. METHODS: For this purpose, we created chemokine receptor 7 (CCR7) expressing porcine SC (NPSCi-CCR7) to facilitate their migration into lymphoid organ in vivo and their potential to modulate systemic immune responses was evaluated using mouse allogeneic skin graft model. RESULTS: Directed migration of NPSCi-CCR7 cells from periphery into lymphoid organs was dramatically promoted compared to control NPSCi cells. Also pre-transplantation of NPSCi-CCR7 significantly suppressed lymphocyte proliferation and prolonged the allogeneic skin graft survival. CONCLUSION: These results suggest that our new strategy to traffic SC to lymphoid organs using CCR7 is very effective and can be extended to traffic other immune modulatory cells or proteins to primary and secondary lymphoid structures to augment their therapeutic potential.