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 function in patients with Parkinson's disease, if immunological rejection could be prevented. This study was performed to investigate the role of natural killer 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 mesencephalon of 26-27-day-old pig embryos, and 2 microl was implanted in the right striata of mutant CD1d1 null (CD1.1-/-) mice, NK1.1-depleted mice, and controls. The CD1.1-/- mice are deficient in NK T cells and the antigen-presenting molecule CD1d1. Graft survival and host responses were determined immunohistochemically using markers for dopamine neurons, CD4-, CD8- cells, microglia, and macrophages. At 2 weeks, the grafts were significantly larger in CD1.1-/- mice, 0.09 +/- 0.02 microl (mean +/- SEM), compared with controls, 0.05 +/- 0.01 microl. There was no significant difference between NK1.1-depleted mice, 0.02 +/- 0.01 microl, and controls. At 5 weeks, two grafts were still present in the CD1-/- mice, whereas only scars remained in the controls and in 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 xenografting, NK1.1+ cells do not seem to be important mediators of the rejection of discordant cellular neural xenografts. However, our results suggest that the antigen-presenting molecule CD1d1 may be involved in the rejection process.
Larsson
L C
LC
Wallenberg Neuroscience Center, Lund University, Sweden. lena.larsson@mphy.lu.se
Anderson
P
P
Widner
H
H
Korsgrent
O
O
D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics*; D055610:Antigens, CD1d; D016380:Brain Tissue Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016332:Fetal Tissue Transplantation; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017628:Microglia / Q000166:cytology / Q000276:immunology; D013552:Swine; D014183:Transplantation, Heterologous
D018949:Antigens, CD1; D055610:Antigens, CD1d