Abstract
Bone marrow transplantation (BMT) is increasingly used to treat Multiple Sclerosis (MS) a CNS inflammatory disease with elevated CNS and systemic IFNγ levels. We wished to determine the effect of IFNγ on BM graft survival in a transgenic mouse model for chronic MS. BM transplantation into transgenic mice which express elevated levels of IFNγ in the CNS was unsuccessful. By contrast, there was 100% survival of even fully allogeneic, T-depleted transplants to transgenics that over express TNFα in the CNS, using the same MBP promoter. IFNγ was detectable in spleen of irradiated mice but levels were higher in IFNγ transgenics. BM transplantation into IFNγ-deficient recipients also had a high failure rate. Transplants of BM from mice lacking expression of IFNγ-receptor failed, whereas IFNγ-deficient grafts survived, suggesting that IFNγ response status of the graft can also positively influence survival. IFNγ therefore has a dual role in BM transplantation and the outcome will depend on relative levels of cytokine expression.
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