Fetal grafting for Parkinson's disease: Expression of immune markers in two patients with functional fetal nigral implants

In a number of centers throughout the world, fetal nigral transplantation is being performed for the treatment of Parkinson's disease (PD). Clinical results have been inconsistent. One parameter that differs among transplant studies is the degree and manner by which patients are immunosuppressed following transplantation. Indeed, the role of the immune system following fetal grafting in humans is not well understood. Recently, two patients from our open label trial that received fetal nigral implants have come to autopsy. These patients were immunosuppressed with cyclosporin for 6 mo posttransplantation and survived for a total of 18 mo postgrafting. Robust survival of grafted dopamine-containing cells was observed in both cases. Immunostaining for HLA-DR revealed a dense collection of cells within grafts from both cases. HLA-DR staining was rarely observed within the host including nongrafted regions of the striatum. A more detailed analysis of immune markers was performed in Case 2. Numerous pan macrophages, T-cells, and B-cells were observed within graft sites located in the postcommissural putamen. In contrast, staining for these immune cells was not observed within the ungrafted anterior putamen. These findings suggest that even in healthy appearing functional nigral implants, grafts are invaded by host immune cells that could compromise their long-term viability and function. Alternatively, immune cells are known to secrete trophic factors, which may ultimately favor graft survival and function. Further work is needed to understand the role of the immune system in fetal grafting.