IMMUNE-RESPONSE AND NEUROTROPHIC FACTOR INTERACTIONS IN PERIPHERAL-NERVE TRANSPLANTS

Several types of immunocompetent cells of hematopoietic origin are inv olved in determining the immunological and regenerative fate of periph eral nerve transplants used for neurosurgical repair, The present stud y compares the immunological fate of nerve isografts and allografts wi th emphasis on the immunobiological events and neurotrophic interactio ns leading to graft survival and nerve fiber regeneration through them . The nerve transplantation model is unique as tissue rejection/inflam mation is observed along with the nerve regeneration process. Nerve gr afts become vascularized within a few days via neovascularization afte r transplantation. This is followed by progressive invasion of host ma crophages and T lymphocytes that recognize the histocompatible antigen s and initiate the rejection response. Two main types of donor residen t cells are involved in early stages of graft rejection. These are mac rophages and Schwann cells. Both of these cells have been found to pos sess antigen-presenting function and also can produce several cytokine s. The most relevant to the peripheral nerves are tumor necrosis facto r (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 ro le in modulating and enhancing of the immune response. Finally, IL-1 i s of special significance because it promotes the expression of nerve growth factor (NGF) by the Schwann cells of the peripheral nerve and i s important for nerve fiber regeneration. NGF in turn has been shown t o enhance macrophage function and inflammatory response. Taken togethe r, these findings show that NGF levels and inflammation in injured tis sue play an important role in determining the success of transplants a nd in tissue repair.