Intracerebral cytokine profiles in adult rats grafted with neural tissue of different immunological disparity.

To understand graft rejection in cell based therapies for brain repair we have quantified IL-1beta, IL-2, IL-4, IL-10, IL-12p40, IFN-gamma and TNF-alpha mRNA levels using real-time PCR, at days 4, 14, and 42 post-transplantation, in rats engrafted with syngeneic, allogeneic, concordant and discordant xenogeneic neural tissues. In addition, in the discordant xenografts immunohistochemistry and in situ hybridization were applied to detect local expression of IFN-gamma, TNF-alpha, IL-10 and TGF-beta. Allografts remained non-rejected but expressed IL-1beta, TNF-alpha and IL-4 transcripts but not IL-12p40 and IFN-gamma. Xenografts demonstrated distinct cytokine profiles that differed from syngeneic and allogeneic grafts. Non-rejected discordant xenografts contained higher levels of TNF-alpha transcripts and lower levels of IL-2 transcripts than the rejected ones at day 42. Discordant xenografts displayed a stronger and earlier expression of IL-1beta and TNF-alpha, followed by T-helper 1 and T-helper 2 associated cytokine expression. The number of cells expressing mRNA encoding TNF-alpha and TGF-beta was significantly increased over time in the discordant group. In conclusion, the immunological disparity of the implanted tissue explains survival rates and is associated with different cytokine profiles. In allografts, a chronic inflammatory reaction was detected and in xenogeneic grafts a delayed hypersensitivity like reaction may be involved in rejection.