Systemic immune response to peripheral nerve transplants across major histocompatibility class-I and class-II barriers.

The use of peripheral nerve transplantation in limb reconstruction has been limited by tissue rejection. In order to identify the major histocompatibility antigens involved in tissue rejection, mutant strains of inbred mice, differing from the parent strain (C57BL/6) by either major histocompatibility complex Class I (B6.C-H2bml mice) or Class II (B6.C-H2bml2 mice), were used in models of nerve transplantation. One, 2, and 3 weeks after nerve or skin transplantation, the immune response in the recipient animal was monitored with use of lymphocyte-dependent cytotoxicity and complement-dependent cytotoxicity assays. Skin transplants were used for comparison as the gold standard of a nonvascularized graft with an easily observable success or failure. There was no significant cellular immune response by the lymphocyte-mediated cytotoxicity assay when nerve or skin transplants involved an isolated Class-I or Class-II mismatch, but there was a significant response 2 weeks after transplantations across a combined Class-I and Class-II barrier for nerve (p < 0.04) or skin (p < 0.03). An antibody response to the grafts occurred for both skin and nerve transplants but only when a combined barrier was involved. This preliminary study, using a mouse model, suggests that nerve transplantation-may be performed without systemic evidence of rejection with only a partial cross match of the major histocompatibility complexes, thus decreasing the complexity of tissue typing necessary for tissue banking.

A comparison of immune response to nerve and skin allografts.

Research in limb reconstruction using peripheral nerve tissue has been hampered by tissue rejection. Not all tissues express major histocompatibility class I and class II antigens to the same extent. Allogenic and isogenic peripheral nerve grafts and split-thickness skin grafts were performed using C57BL/6 and Balb/c mice, which are inbred strains that differ at both major histocompatibility (MHC) class I and class II antigens. The cellular and humoral immune responses of the nerve transplants were compared with studies of skin transplants. Skin allografts represent a "gold standard": they are clearly rejected, with a tissue failure that is easily observed and closely correlated with cellular and humoral projection responses. A significant cellular immune response was noted following both the nerve (p < .04) and skin (p < .03) allografts. The peak response occurred by day 14 following the transplantation. The humoral response with rising antibody titers followed a similar pattern, with peak response at 14 and 21 days post-transplantation. Isogenic transplants did not produce a cellular or humoral immune responses. There was no significant difference between the immune responses produced by the skin transplants, compared to the nerve transplants. Because of the difficulty in producing accurate models of animal function following nerve transplantation, quantitative studies of host immune response to transplantation have not correlated well with the recipient's final functional result. A comparison of the immune responses between clearly rejected skin allografts and nerve allografts suggests that the immune response resulting from nerve allografts could decrease the functional performance of the nerve grafts.(ABSTRACT TRUNCATED AT 250 WORDS)