Improved graft survival and functioning

Graft rejection is frequently preceded by a massive infiltration of both T cells and macrophages. For that reason several studies focused on the effects of macrophage depletion on infiltration of T cells and macrophages in grafted tissues and on graft rejection.

Macrophages are found in large numbers in rejected corneal allografts in rats. In animals treated post-operatively with subconjunctival injections of liposome-encapsulated clodronate at the time of transplantation and several times thereafter, grafts were not rejected during the maximum follow-up of 100 days (32). Cellular infiltration in these grafts was clearly reduced and there was a strong reduction in neovascularization of the cornea. Corneal grafts in rats belonging to control groups that had received empty liposomes (containing phosphate-buffered saline only) and those that had been given no additional treatment were rejected within the usual period of 17 days. These results confirm that macrophages play a crucial role in corneal allograft rejection.

Other recent studies have shown that macrophages are required for T cell infiltration and rejection of fetal pig pancreas xenografts in NOD mice (33). Also, it has been shown that macrophages have a central role in the development and activation of B cell-cytotoxic T cells that cause B cell destruction resulting in auto-immune diabetes in NOD mice (34). Suppression of macrophage activity by clodronate-liposomes as a tool to improve graft survival and functioning is currently investigated in several laboratories.

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