Discordant neural tissue xenografts survive longer in immunoglobulin deficient mice

Background. The immune response against discordant xenografts in the brain is incompletely understood and remains a major obstacle for future clinical applications of xenogeneic neural tissue transplants in neurodegenerative disorders. To determine the role of antibodies in the rejection process, we compared graft survival and immune reactions between immunoglobulin defici ent (IgKO) and normal mice. Methods. A cell suspension of embryonic porcine ventral mesencephalon was i njected into the striatum of adult normal and IgKO mice. Graft sizes and nu mber of infiltrating CD4- and CD8-positive lymphocytes were determined by s tereological methods at 4 days and 2, 4, and 6 weeks after the transplants. Microglial accumulation was determined using the optical densitometrical m ethod, Intraparenchymal deposition of IgG was investigated at 4 days and 2 weeks. Results, The majority of IgKO mice had surviving grafts for up to 4 weeks, whereas survival was minimal in control mice beyond 4 days. Graft sizes dif fered significantly between IgKO and control mice at 2 weeks (P<0.01, Krusk al Wallis ANOVA, followed by Mann Whitney test), The majority of infiltrati ng lymphocytes were CD4-positive in control mice but CD8-positive in IgKO m ice. Microglial accumulation was strong around surviving grafts in IgKO mic e at 4 weeks. Prominent staining of IgG, diffuse in the transplanted hemisp here and specific on grafted neurons, was found in control mice. Conclusions, Our results suggest that immunoglobulins play an initiating ro le in rejection of discordant neural xenografts, After a prolonged graft su rvival of approximately 4 weeks, a cellular response with a large proportio n CD8-positive cells leads to rejection in IgKO mice.