Regulatory Dendritic Cell Infusion Prolongs Kidney Allograft Survival in Nonhuman Primates
Article first published online: 11 JUN 2013
© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons
American Journal of Transplantation
Volume 13, Issue 8, pages 1989–2005, August 2013
How to Cite
Ezzelarab, M. B., Zahorchak, A. F., Lu, L., Morelli, A. E., Chalasani, G., Demetris, A. J., Lakkis, F. G., Wijkstrom, M., Murase, N., Humar, A., Shapiro, R., Cooper, D. K. C. and Thomson, A. W. (2013), Regulatory Dendritic Cell Infusion Prolongs Kidney Allograft Survival in Nonhuman Primates. American Journal of Transplantation, 13: 1989–2005. doi: 10.1111/ajt.12310
- Issue published online: 26 JUL 2013
- Article first published online: 11 JUN 2013
- Manuscript Accepted: 16 APR 2013
- Manuscript Revised: 3 APR 2013
- Manuscript Received: 14 FEB 2013
- National Institutes of Health grant U01 AI051698
Additional supporting information may be found in the online version of this article.
Figure S1: Renal allograft histology. (A) Termination graft histology of M45 (DCreg group; left) euthanized on Day 118 demonstrates more severe and widespread inflammation, interstitial fibrosis and tubular atrophy than M145 graft (control group; right) euthanized 66 days earlier on Day 52. Both show evidence of active tubulitis, as illustrated in the inserts. Low magnification images are 2× and the higher power inserts are 20×. (B) Graft biopsy from M113 (DCreg group) on Day 280 posttransplant (100 days after stopping immunosuppression) showing moderate to severe interstitial inflammation with active tubulitis. The insert (right) illustrates the area immediately above the (*) at higher magnification to illustrate the tubulitis and the focal peritubular capillaritis. Low magnification is 5× and the higher power insert is 60×.
Figure S2: DCreg infusion does not elicit circulating anti-donor alloAbs in renal-transplanted monkeys. Circulating anti-donor IgM and IgG alloAb levels were determined by flow cytometric analysis, as described in the Materials and Methods, before and at various times after transplant in control and DCreg-treated renal-allografted monkeys. Normal human serum served as a positive control. (A) Histograms are representative data of one recipient from each group. (B) MFI (mean florescence intensity) of IgM and IgG Abs binding to donor cells from all 6 transplant recipients in each group. Samples were collected before transplantation and 4–8 weeks after transplantation depending on the time of euthanasia. Bars indicate mean ± SD.
Figure S3: DCreg infusion does not affect the incidence of circulating Treg but reduces the Tmem:Treg ratio in transplanted monkeys. (A) Circulating levels of CD4+CD25+CD127loFoxp3+ Treg in control (n = 6) and DCreg-treated renal allografts recipients (n = 6), before and at various times post transplant. Data are means ± SD. (B) Reduced ratio of circulating CD4+CD95+ Tmem:Treg during prolonged graft survival in a DCreg-infused monkey (M113), followed by augmented ratio at the time of rejection.
Table S1: Propagation of DCreg from single leukapheresis products of 6 donor rhesus monkeys
Please note: Wiley Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.