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 Gaynor, Bonnie B Blomberg, Anne Rosen, Gary Kleiner, Camillo Ricordi, Joshua Miller

Research output: Contribution to journalArticle

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

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Chimerism
Bone Marrow
Tissue Donors
Lymphocytes
Transplants
Kidney
Messenger RNA
Phenotype
Regulatory T-Lymphocytes
Immunosuppression
Chronic Kidney Failure
Real-Time Polymerase Chain Reaction
Healthy Volunteers
Flow Cytometry
Demography
Transplant Recipients

Keywords

  • Bone marrow
  • FoxP3
  • Regulatory cells
  • Renal transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Cirocco, R. E., Carreño, M. R., Mathew, J. M., Garcia-Morales, R. O., Fuller, L., Esquenazi, V., ... 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

FoxP3 mRNA transcripts and regulatory cells in renal transplant recipients 10 years after donor marrow infusion. / Cirocco, Robert E.; Carreño, Manuel R.; Mathew, James M.; Garcia-Morales, Rolando O.; Fuller, Laphalle; Esquenazi, Violet; Ciancio, Gaetano; Burke, George W; Gaynor, Jeffrey; Blomberg, Bonnie B; Rosen, Anne; Kleiner, Gary; Ricordi, Camillo; Miller, Joshua.

In: Transplantation, Vol. 83, No. 12, 01.06.2007, p. 1611-1619.

Research output: Contribution to journalArticle

Cirocco, RE, Carreño, MR, Mathew, JM, Garcia-Morales, RO, Fuller, L, Esquenazi, V, Ciancio, G, Burke, GW, Gaynor, J, Blomberg, BB, 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, vol. 83, no. 12, pp. 1611-1619. https://doi.org/10.1097/01.tp.0000266908.37446.02
Cirocco RE, Carreño MR, Mathew JM, Garcia-Morales RO, Fuller L, Esquenazi V et al. FoxP3 mRNA transcripts and regulatory cells in renal transplant recipients 10 years after donor marrow infusion. Transplantation. 2007 Jun 1;83(12):1611-1619. https://doi.org/10.1097/01.tp.0000266908.37446.02
Cirocco, Robert E. ; Carreño, Manuel R. ; Mathew, James M. ; Garcia-Morales, Rolando O. ; Fuller, Laphalle ; Esquenazi, Violet ; Ciancio, Gaetano ; Burke, George W ; Gaynor, Jeffrey ; Blomberg, Bonnie B ; Rosen, Anne ; Kleiner, Gary ; Ricordi, Camillo ; Miller, Joshua. / FoxP3 mRNA transcripts and regulatory cells in renal transplant recipients 10 years after donor marrow infusion. In: Transplantation. 2007 ; Vol. 83, No. 12. pp. 1611-1619.
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AU - Cirocco, Robert E.

AU - Carreño, Manuel R.

AU - Mathew, James M.

AU - Garcia-Morales, Rolando O.

AU - Fuller, Laphalle

AU - Esquenazi, Violet

AU - Ciancio, Gaetano

AU - Burke, George W

AU - Gaynor, Jeffrey

AU - Blomberg, Bonnie B

AU - Rosen, Anne

AU - Kleiner, Gary

AU - Ricordi, Camillo

AU - Miller, Joshua

PY - 2007/6/1

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N2 - 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.

AB - 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.

KW - Bone marrow

KW - FoxP3

KW - Regulatory cells

KW - Renal transplantation

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