Enhanced survival of porcine neural xenografts in mice lacking CD1d1, but no effect of NK1.1 depletion

Transplantation of embryonic porcine neurons may restore neurological funct ion in patients with Parkinson's disease, if immunological rejection could be prevented. This study was performed to investigate the role of natural k iller cells (NK cells) and NK1.1+ T cells (NK T cells) in the rejection of neural xenografts. A cell suspension was prepared from the ventral mesencep halon of 26-27-day-old pig embryos, and 2 mul was implanted in the right st riata of mutant CD1d1 null (CD1.1-/-) mice, NK1.1-depleted mice, and contro ls. The CD1.1-/- mice are deficient in NK T cells and the antigen-presentin g molecule CD1d1. Graft survival and host responses were determined immunoh istochemically using markers for dopamine neurons, CD4-, CD8- cells, microg lia, and macrophages. At 2 weeks, the grafts were significantly larger in C D1.1-/- mice, 0.09 +/- 0.02 mul (mean +/- SEM), compared with controls, 0.0 5 +/- 0.01 mul. There was no significant difference between NK1.1-depleted mice, 0.02 +/- 0.01 mul, and controls. At 5 weeks, two grafts were still pr esent in the CD1-/- mice, whereas only scars remained in the controls and i n the NK1.1-depleted mice, immune reactions were strong at 2 weeks and less pronounced at 5 weeks in all groups. Microglial activation was lower in NK -depleted mice than in the controls at 2 weeks. In contrast to organ xenogr afting, NK1.1+ cells do not seem to be important mediators of the rejection of discordant cellular neural xenografts. However, our results suggest tha t the antigen-presenting molecule CD1d1 may be involved in the rejection pr ocess.