Regulatory T-cell Subset Analysis and Profile of Interleukin (IL)-10, IL-17 and Interferon-gamma Cytokine-producing Cells in Kidney Allograft Recipients with Donor Cells Infusion

Overview

Journal Clin Exp Nephrol

Publisher Springer

Specialty Nephrology

Date 2012 Feb 9

PMID 22314659

Citations 7

Authors

Moslem Ranjbar

Ghasem Solgi

Mousa Mohammadnia

Behrouz Nikbin

Gholamreza Pourmand

Bita Ansaripour

Aliakbar Amirzargar

Affiliations

Soon will be listed here.

Abstract

Background: This pilot study aimed to assess whether the perioperative infusion of donor bone marrow cells (DBMC) in renal allograft recipients can affect the appearance of peripheral regulatory T-cell subsets and the profile of cytokine-producing cells [interferon-gamma (IFN-γ), interleukin (IL)-17 and IL-10] 2 years after transplantation.

Methods: Fresh blood samples were collected from 14 kidney recipients who received infusion and from 13 kidney recipients without infusion who served as controls at the end of the second post-transplantation year. Initially the percentages of CD4(+)CD25(+)FoxP3(+) T cells and CD3(+)CD8(+)CD28(-) T cells were quantified using flowcytometry. Thereafter, the frequencies of IL-10-, IL-17- and IFN-γ-producing cells were determined separately using the ELISPOT technique with peptides corresponding to mismatched donor HLA-DR molecules and phytohemagglutinin (PHA).

Results: The mean numbers of IFN-γ- and IL-17-producing cells in response to PHA were lower in infused patients than in controls (P = 0.02 and P = 0.18, respectively); however, an increased frequency of IL-10-producing cells was observed compared to controls (P = 0.07). Furthermore, the ratio of IL-10/IFN-γ-producing cells was significantly higher in the DBMC-infused group versus controls (P = 0.01). There was a negative correlation between the percentage of CD3(+)CD8(+)CD28(-)T cells and IL-17-producing cells in the infused group (r = -0.539, P = 0.04). The mean levels and the frequency of microchimerism within the first post-transplantation year were also significantly higher in infused patients than in controls (P = 0.007 and P = 0.001, respectively).

Conclusion: Our findings suggest that DBMC infusion could partially stimulate the regulatory mechanisms against alloimmune responses in kidney allograft recipients

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References

Ciancio G, Burke G, Garcia-Morales R, Suzart K, Rosen A, Ricordi C . Effect of living-related donor bone marrow infusion on chimerism and in vitro immunoregulatory activity in kidney transplant recipients. Transplantation. 2002; 74(4):488-96. DOI: 10.1097/00007890-200208270-00010. View

Garcia-Morales R, Esquenazi V, Zucker K, Gomez C, Fuller L, Carreno M . An assessment of the effects of cadaver donor bone marrow on kidney allograft recipient blood cell chimerism by a novel technique combining PCR and flow cytometry. Transplantation. 1996; 62(8):1149-60. DOI: 10.1097/00007890-199610270-00021. View

Chadha R, Heidt S, Jones N, Wood K . Th17: contributors to allograft rejection and a barrier to the induction of transplantation tolerance?. Transplantation. 2011; 91(9):939-45. DOI: 10.1097/TP.0b013e3182126eeb. View

Spitzer T, Delmonico F, Tolkoff-Rubin N, McAfee S, Sackstein R, Saidman S . Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal transplantation for multiple myeloma with end stage renal disease: the induction of allograft tolerance through mixed lymphohematopoietic chimerism. Transplantation. 1999; 68(4):480-4. DOI: 10.1097/00007890-199908270-00006. View

Tsaur I, Gasser M, Aviles B, Lutz J, Lutz L, Grimm M . Donor antigen-specific regulatory T-cell function affects outcome in kidney transplant recipients. Kidney Int. 2011; 79(9):1005-12. DOI: 10.1038/ki.2010.533. View

Hara M, Kingsley C, Niimi M, Read S, Turvey S, Bushell A . IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo. J Immunol. 2001; 166(6):3789-96. DOI: 10.4049/jimmunol.166.6.3789. View

Akl A, Jones N, Rogers N, Bakr M, Mostafa A, El Shehawy E . An investigation to assess the potential of CD25highCD4+ T cells to regulate responses to donor alloantigens in clinically stable renal transplant recipients. Transpl Int. 2007; 21(1):65-73. DOI: 10.1111/j.1432-2277.2007.00560.x. View

Seung E, Mordes J, Rossini A, Greiner D . Hematopoietic chimerism and central tolerance created by peripheral-tolerance induction without myeloablative conditioning. J Clin Invest. 2003; 112(5):795-808. PMC: 182209. DOI: 10.1172/JCI18599. View

Delis S, Ciancio G, Burke 3rd G, Garcia-Morales R, Miller J . Donor bone marrow transplantation: chimerism and tolerance. Transpl Immunol. 2004; 13(2):105-15. DOI: 10.1016/j.trim.2004.05.006. View

10.

Hendrikx T, van Gurp E, Sewgobind V, Mol W, Schoordijk W, Klepper M . Generation of donor-specific regulatory T-cell function in kidney transplant patients. Transplantation. 2009; 87(3):376-83. DOI: 10.1097/TP.0b013e3181901b69. View

11.

Mitchell P, Afzali B, Lombardi G, Lechler R . The T helper 17-regulatory T cell axis in transplant rejection and tolerance. Curr Opin Organ Transplant. 2009; 14(4):326-31. DOI: 10.1097/MOT.0b013e32832ce88e. View

12.

Kingsley C, Karim M, Bushell A, Wood K . CD25+CD4+ regulatory T cells prevent graft rejection: CTLA-4- and IL-10-dependent immunoregulation of alloresponses. J Immunol. 2002; 168(3):1080-6. DOI: 10.4049/jimmunol.168.3.1080. View

13.

Monaco A . The beginning of clinical tolerance in solid organ allografts. Exp Clin Transplant. 2005; 2(1):153-61. View

14.

Najafian N, Salama A, Fedoseyeva E, Benichou G, Sayegh M . Enzyme-linked immunosorbent spot assay analysis of peripheral blood lymphocyte reactivity to donor HLA-DR peptides: potential novel assay for prediction of outcomes for renal transplant recipients. J Am Soc Nephrol. 2001; 13(1):252-259. DOI: 10.1681/ASN.V131252. View

15.

Bonilla W, Geuking M, Aichele P, Ludewig B, Hengartner H, Zinkernagel R . Microchimerism maintains deletion of the donor cell-specific CD8+ T cell repertoire. J Clin Invest. 2006; 116(1):156-62. PMC: 1323267. DOI: 10.1172/JCI26565. View

16.

Mittal S, Sharma R, Gupta A, Naik S . Increased interleukin-10 production without expansion of CD4+CD25+ T-regulatory cells in early stable renal transplant patients on calcineurin inhibitors. Transplantation. 2009; 88(3):435-41. DOI: 10.1097/TP.0b013e3181af20fd. View

17.

Taflin C, Nochy D, Hill G, Frouget T, Rioux N, Verine J . Regulatory T cells in kidney allograft infiltrates correlate with initial inflammation and graft function. Transplantation. 2010; 89(2):194-9. DOI: 10.1097/TP.0b013e3181c3ca11. View

18.

Scandling J, Busque S, Dejbakhsh-Jones S, Benike C, Millan M, Shizuru J . Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med. 2008; 358(4):362-8. DOI: 10.1056/NEJMoa074191. View

19.

Salama A, Najafian N, Clarkson M, Harmon W, Sayegh M . Regulatory CD25+ T cells in human kidney transplant recipients. J Am Soc Nephrol. 2003; 14(6):1643-51. DOI: 10.1097/01.asn.0000057540.98231.c1. View

20.

Solgi G, Mytilineos J, Gadi V, Paul B, Pourmand G, Mehrsai A . Donor-derived peripheral mononuclear cell DNA is associated with stable kidney allograft function: a randomized controlled trial. Chimerism. 2012; 2(4):102-10. PMC: 3321880. DOI: 10.4161/chim.2.4.19095. View