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Immune Recovery

Reconstitution of regulatory T-cell subsets after allogeneic hematopoietic SCT

Bone Marrow Transplantation volume 49, pages 1089–1092 (2014)Cite this article

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Abstract

Previous studies on regulatory T-cell (Treg) reconstitution after allogeneic hematopoietic SCT (HSCT) have suggested that, within the GVHD process, imbalance between effector T cells and Tregs may be more important than the absolute numbers of circulating Tregs. No study has analyzed naive vs memory Treg reconstitution in a longitudinal cohort with large numbers of patients. The reconstitution of total and subsets of Treg was prospectively analyzed by flow cytometry in 185 consecutive recipients at 3, 6, 12 and 24 months after allogeneic HSCT. The levels of total, naive and memory Tregs increased, mainly within the memory subset, but remained lower than healthy controls up to 2 years after transplantation. Reduced-intensity conditioning and peripheral blood (PBSC) as the source of stem cells were associated with better 3-month reconstitution. In multivariate analysis, PBSC, recipient age ⩽25 and no anti-thymoglobulin in the conditioning regimen were associated with a better Treg reconstitution. Naive Treg long-term reconstitution was mainly influenced by recipient age. Whereas prior acute GVHD impaired Treg reconstitution, Treg subsets (absolute numbers and frequencies relative to CD4+ T-cell subsets) at 3, 6 and 12 months after HSCT were not associated with the occurrence of a later episode of chronic GVHD.

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References

  1. Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S et al. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med 2003; 9: 1144–1150.

    Article  CAS  Google Scholar 

  2. Di Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood 2011; 117: 3921–3928.

    Article  CAS  Google Scholar 

  3. Brunstein CG, Miller JS, Cao Q, McKenna DH, Hippen KL, Curtsinger J et al. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood 2011; 117: 1061–1070.

    Article  CAS  Google Scholar 

  4. Ukena SN, Grosse J, Mischak-Weissinger E, Buchholz S, Stadler M, Ganser A et al. Acute but not chronic graft-versus-host disease is associated with a reduction of circulating CD4(+)CD25 (high)CD127 (low/-) regulatory T cells. Ann Hematol 2011; 90: 213–218.

    Article  CAS  Google Scholar 

  5. Matthews K, Lim Z, Afzali B, Pearce L, Abdallah A, Kordasti S et al. Imbalance of effector and regulatory CD4 T cells is associated with graft-versus-host disease after hematopoietic stem cell transplantation using a reduced intensity conditioning regimen and alemtuzumab. Haematologica 2009; 94: 956–966.

    Article  CAS  Google Scholar 

  6. Magenau JM, Qin X, Tawara I, Rogers CE, Kitko C, Schlough M et al. Frequency of CD4(+)CD25(hi)FOXP3(+) regulatory T cells has diagnostic and prognostic value as a biomarker for acute graft-versus-host-disease. Biol Blood Marrow Transplant 2010; 16: 907–914.

    Article  Google Scholar 

  7. Matsuoka K, Kim HT, McDonough S, Bascug G, Warshauer B, Koreth J et al. Altered regulatory T cell homeostasis in patients with CD4+ lymphopenia following allogeneic hematopoietic stem cell transplantation. J Clin Invest 2010; 120: 1479–1493.

    Article  CAS  Google Scholar 

  8. Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, Niwa A et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 2009; 30: 899–911.

    Article  CAS  Google Scholar 

  9. Corre E, Carmagnat M, Busson M, de Latour RP, Robin M, Ribaud P et al. Long-term immune deficiency after allogeneic stem cell transplantation: B-cell deficiency is associated with late infections. Haematologica 2010; 95: 1025–1029.

    Article  Google Scholar 

  10. Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 2006; 203: 1701–1711.

    Article  CAS  Google Scholar 

  11. Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A . Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 1999; 401: 708–712.

    Article  CAS  Google Scholar 

  12. Charrier E, Cordeiro P, Brito RM, Mezziani S, Herblot S, Le Deist F et al. Reconstitution of maturating and regulatory lymphocyte subsets after cord blood and BMT in children. Bone Marrow Transplant 2013; 48: 376–382.

    Article  CAS  Google Scholar 

  13. Kanda J, Chiou LW, Szabolcs P, Sempowski GD, Rizzieri DA, Long GD et al. Immune recovery in adult patients after myeloablative dual umbilical cord blood, matched sibling, and matched unrelated donor hematopoietic cell transplantation. Biol Blood Marrow Transplant 2012; 18: 1664–1676 e1.

    Article  CAS  Google Scholar 

  14. Jacobson CA, Turki AT, McDonough SM, Stevenson KE, Kim HT, Kao G et al. Immune reconstitution after double umbilical cord blood stem cell transplantation: comparison with unrelated peripheral blood stem cell transplantation. Biol Blood Marrow Transplant 2012; 18: 565–574.

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Service d’Hématologie Greffe, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France

    A Xhaard, M Robin, P Ribaud, N Dhedin, S Abbes, R Peffault de Latour & G Socié

  2. Laboratoire d’Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France

    H Moins-Teisserenc, M Carmagnat, V-D Kheav, G Maki & A Toubert

  3. Inserm UMRS-940, Institut Universitaire d’Hématologie, Paris, France

    H Moins-Teisserenc, M Busson, A Toubert & G Socié

  4. Université Paris-Diderot et Paris Sorbonne Cité, Paris, France

    H Moins-Teisserenc, V-D Kheav, A Toubert & G Socié

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  1. A Xhaard
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  2. H Moins-Teisserenc
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  3. M Busson
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  4. M Robin
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  5. P Ribaud
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  6. N Dhedin
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  7. S Abbes
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  8. M Carmagnat
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Correspondence to G Socié.

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Xhaard, A., Moins-Teisserenc, H., Busson, M. et al. Reconstitution of regulatory T-cell subsets after allogeneic hematopoietic SCT. Bone Marrow Transplant 49, 1089–1092 (2014). https://doi.org/10.1038/bmt.2014.105

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  • DOI: https://doi.org/10.1038/bmt.2014.105

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