Subscribe to RSS
DOI: 10.1055/s-0029-1247081
Allogeneic porcine CD4+CD25+ T cells regulate the development of transplant arteriosclerosis in porcinized mice
We showed that graft acceptance correlated with the frequency of CD4+CD25+ regulatory T cells in a porcine lung transplantation model. However, it is unknown, if this type of T cell regulation is the cause for or merely an epiphenomenon of allograft survival. Thus, we implanted porcine arteries and adoptively transferred porcine PBMC into NODrag-/-gammac-/- mice.
Porcine intercostal arteries were implanted into the murine abdominal aorta. Animals received either 10×106 autologous (Group A), or allogeneic PBMC (Group B, graft and cells were obtained from two MHC mismatched pigs), group C received allogeneic PBMC depleted of CD4+CD25+ cells, whereas group D recipients received allogeneic PBMC augmented with additional CD4+CD25+ T cells. Porcine CD45+ cell engraftment was monitored by FACS postoperatively. Transplant arteriosclerosis was histologically assessed on postoperative day (POD) 28. Quantification was done by measuring intima to media ratio.
All groups showed good porcine cell engraftment as monitored by FACS on POD 14 and 28. Transplant arteriosclerosis was different among groups (p<0.05) and severely pronounced in group C. Mean intima to media ratio was higher (p<0.05) in group C as compared to groups A and B, respectively (80.3±11.6% vs. 23.8±5.2% and 47.7±13.6%). Addition of CD4+CD25+ T cells in group D resulted in a marked reduction of the mean intima to media ratio towards the level of the control group A (23.0±7.0%).
Firstly, regulatory T cells control the development of transplant arteriosclerosis in vivo. Secondly, our model enables the functional study of allogeneic T cell regulation in large animals and humans.