Immune response and neurotrophic factor interactions in peripheral nerve transplants.

Several types of immunocompetent cells of hematopoietic origin are involved in determining the immunological and regenerative fate of peripheral nerve transplants used for neurosurgical repair. The present study compares the immunological fate of nerve isografts and allografts with emphasis on the immunobiological events and neurotrophic interactions leading to graft survival and nerve fiber regeneration through them. The nerve transplantation model is unique as tissue rejection/inflammation is observed along with the nerve regeneration process. Nerve grafts become vascularized within a few days via neovascularization after transplantation. This is followed by progressive invasion of host macrophages and T lymphocytes that recognize the histocompatible antigens and initiate the rejection response. Two main types of donor resident cells are involved in early stages of graft rejection. These are macrophages and Schwann cells. Both of these cells have been found to possess antigen-presenting function and also can produce several cytokines. The most relevant to the peripheral nerves are tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1), interferon-gamma (IFN-gamma) and IL-12. TNF-alpha in addition to its capacity to kill cells is involved in activation of macrophages. IL-12 and IFN-gamma have a potential role in modulating and enhancing of the immune response. Finally, IL-1 is of special significance because it promotes the expression of nerve growth factor (NGF) by the Schwann cells of the peripheral nerve and is important for nerve fiber regeneration. NGF in turn has been shown to enhance macrophage function and inflammatory response. Taken together, these findings show that NGF levels and inflammation in injured tissue play an important role in determining the success of transplants and in tissue repair.