Adoptive transfer of T-cell precursors enhances T-cell reconstitution after allogeneic hematopoietic stem cell transplantation Journal Article


Authors: Zakrzewski, J. L.; Kochman, A. A.; Lu, S. X.; Terwey, T. H.; Kim, T. D.; Hubbard, V. M.; Muriglan, S. J.; Suh, D.; Smith, O. M.; Grubin, J.; Patel, N.; Chow, A.; Cabrera-Perez, J.; Radhakrishnan, R.; Diab, A.; Perales, M. A.; Rizzuto, G.; Menet, E.; Pamer, E. G.; Heller, G.; Zúñiga-Pflücker, J. C.; Alpdogan, O.; van den Brink, M. R. M.
Article Title: Adoptive transfer of T-cell precursors enhances T-cell reconstitution after allogeneic hematopoietic stem cell transplantation
Abstract: Immunoincompetence after allogeneic hematopoietic stem cell transplantation (HSCT) affects in particular the T-cell lineage and is associated with an increased risk for infections, graft failure and malignant relapse. To generate large numbers of T-cell precursors for adoptive therapy, we cultured mouse hematopoietic stem cells (HSCs) in vitro on OP9 mouse stromal cells expressing the Notch-1 ligand Delta-like-1 (OP9-DL1). We infused these cells, together with T-cell-depleted mouse bone marrow or purified HSCs, into lethally irradiated allogeneic recipients and determined their effect on T-cell reconstitution after transplantation. Recipients of OP9-DL1-derived T-cell precursors showed increased thymic cellularity and substantially improved donor T-cell chimerism (versus recipients of bone marrow or HSCs only). OP9-DL1-derived T-cell precursors gave rise to host-tolerant CD4 + and CD8 + populations with normal T-cell antigen receptor repertoires, cytokine secretion and proliferative responses to antigen. Administration of OP9-DL1-derived T-cell precursors increased resistance to infection with Listeria monocytogenes and mediated significant graft-versus-tumor (GVT) activity but not graft-versus-host disease (GVHD). We conclude that the adoptive transfer of OP9-DL1-derived T-cell precursors markedly enhances T-cell reconstitution after transplantation, resulting in GVT activity without GVHD. © 2006 Nature Publishing Group.
Keywords: controlled study; nonhuman; cd8+ t lymphocyte; cell proliferation; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; bone marrow; hematopoietic stem cell transplantation; chimera; regeneration; cytokine; graft versus host reaction; stem cells; allogeneic hematopoietic stem cell transplantation; adoptive transfer; cd4 lymphocyte count; cytokine release; graft vs host disease; graft vs tumor effect; lymphocyte depletion; fibroblast growth factor 7; listeriosis; listeria monocytogenes; listeria infections; coculture techniques; t lymphocyte antigen
Journal Title: Nature Medicine
Volume: 12
Issue: 9
ISSN: 1078-8956
Publisher: Nature Publishing Group  
Date Published: 2006-09-01
Start Page: 1039
End Page: 1047
Language: English
DOI: 10.1038/nm1463
PUBMED: 16936725
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 61" - "Export Date: 4 June 2012" - "CODEN: NAMEF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Theo Daniel Kim
    14 Kim
  2. Glenn Heller
    299 Heller
  3. Ewa Menet
    3 Menet
  4. Eric Pamer
    249 Pamer
  5. Adi Diab
    25 Diab
  6. Miguel-Angel Perales
    378 Perales
  7. Sydney X Lu
    51 Lu
  8. Theis Helge Terwey
    17 Terwey
  9. Odette Marsinay Smith
    95 Smith
  10. David Suh
    41 Suh
  11. Adam Kochman
    45 Kochman
  12. Vanessa Marie Hubbard
    42 Hubbard
  13. Gabrielle A Rizzuto
    21 Rizzuto
  14. Jeremy Grubin
    10 Grubin
  15. Neel Patel
    7 Patel