FoxP3 mRNA transcripts and regulatory cells in renal transplant recipients 10 years after donor marrow infusion

Robert E. Cirocco, Manuel R. Carreño, James M. Mathew, Rolando O. Garcia-Morales, Laphalle Fuller, Violet Esquenazi, Gaetano Ciancio, George W. Burke, Jeffrey J. Gaynor, Bonnie B. Blomberg, Anne Rosen, Gary Kleiner, Camillo Ricordi, Joshua Miller

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

BACKGROUND. We update more favorable 10-year deceased donor kidney transplant survival in 63 recipients infused perioperatively with donor vertebral body bone marrow (DBMC-i) vs. 219 noninfused controls having equivalent immunosuppression and demographics. We questioned if this was associated with putatively regulatory FoxP3 mRNA and cell phenotypes (CD4CD25 percentages and high DC2:DC1 ratios) in DBMC-i vs. noninfused controls. METHODS. Baseline studies were performed on peripheral blood lymphocytes (PBLs) vs. marrow in normal laboratory volunteers of CD4CD25 percentages and DC2:DC1 by flow cytometry, and FoxP3 mRNA in CD3 cells by real-time polymerase chain reaction. Similar studies were performed on PBL of the majority of the 10-year patients remaining with graft function: 21 (of the remaining 37) DBMC-i vs. 55 (of the remaining 105) controls. RESULTS. In normal subjects, all parameters were significantly higher in marrow than in PBL, supporting our previous reports of ex vivo DBMC immunoregulation. At 9.8±.02 years posttransplant in DBMC-i vs. controls, death-censored percent graft failure was 17.5% vs. 32.9% (P=0.02) with 247.6±24 vs. 79.9±3.1 (mean±SE) FoxP3 copies/5,000 CD3 cells (P=0.0001). PBL CD4CD25 percentages were lower, but DC2:DC1 values higher in both recipient groups than in end-stage renal disease patients who had lower FoxP3 levels (40.8±5.9, P<0.0001), consistent with non-CD4CD25 T regulatory cells generated long-term posttransplant. Individual higher FoxP3 values correlated with higher iliac crest chimerism in DBMC-i, but not in controls (with 50-fold lower chimerism). In chronically rejecting controls, FoxP3 was further decreased. CONCLUSIONS. Peritransplant DBMC-i has higher 10-year renal transplant acceptance, chimerism, and FoxP3 mRNA in thus-far unclarified regulatory cell phenotypes.

Original languageEnglish (US)
Pages (from-to)1611-1619
Number of pages9
JournalTransplantation
Volume83
Issue number12
DOIs
StatePublished - Jun 1 2007

Keywords

  • Bone marrow
  • FoxP3
  • Regulatory cells
  • Renal transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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    Cirocco, R. E., Carreño, M. R., Mathew, J. M., Garcia-Morales, R. O., Fuller, L., Esquenazi, V., Ciancio, G., Burke, G. W., Gaynor, J. J., Blomberg, B. B., Rosen, A., Kleiner, G., Ricordi, C., & Miller, J. (2007). FoxP3 mRNA transcripts and regulatory cells in renal transplant recipients 10 years after donor marrow infusion. Transplantation, 83(12), 1611-1619. https://doi.org/10.1097/01.tp.0000266908.37446.02