Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Lymphoid Reconstitution

Recovery of lymphocyte and dendritic cell subsets after autologous CD34+ cell transplantation

Bone Marrow Transplantation volume 25, pages 1249–1255 (2000)Cite this article

Abstract

Following high-dose chemotherapy (HDC) and peripheral blood progenitor cell transplantation (PBPCT), there are profound changes in leukocyte homeostasis and the immune system is compromised. Transplantation of purified CD34+ cells may further compromise immune recovery because the grafts are depleted of mature immune cells. However, a detailed monitoring of immune cell reconstitution has not been done. We monitored blood levels of antigen-presenting cells (APC) and of lymphocytes by multi-color flow cytometry at different times post CD34+ PBPCT. We found a rapid normalization of circulating levels of the antigen-presenting CD11c+ dendritic cells (defined as lineage− HLA-DR+ CD11c+ cells). There was a slight over-representation of lin− DR+ CD11c− cells at day 42 post transplantation suggesting that the composition of the APC population might be affected. Normal levels of total T, B and NK lymphocytes were rapidly achieved but the composition of the T cell population was abnormal. Patients had elevated levels of CD8+ T cells at early times and a persistent reduction in levels of naive CD8+ T cells (CD8+ CD4− CD45RA+ CD27+) and of naive CD4+ T cells (CD4+CD3+ CD8− CD45RA+). Thus, we found a rapid recovery of DC after CD34+ PBPCT but the specific numerical defects in naive T cells are likely to be a major cause of immune dysfunction in the patients. Bone Marrow Transplantation (2000) 25, 1249–1255.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Peters WP, Ross M, Vredenburgh J et al. Role of cytokines in autologous bone marrow transplantation Hematol/Oncol Clin North Am 1993 7: 737–747

    Article  CAS  Google Scholar 

  2. Guillaume T, Rubinstein DB, Symann M . Immune reconstitution and immunotherapy after autologous hematopoietic stem cell transplantation Blood 1998 5: 1471–1490

    Google Scholar 

  3. Mackall CL, Fleisher T, Brown M et al. Age, thymopoiesis and CD4+ T-lymphocyte regeneration after intensive chemotherapy New Engl J Med 1995 332: 143–149

    Article  CAS  Google Scholar 

  4. Mackall C, Fleisher T, Brown M et al. Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in prolonged T-cell subset imbalance after intensive chemotherapy Blood 1997 89: 3700–3707

    CAS  PubMed  Google Scholar 

  5. Singh R, Varney M, Buyukberber S et al. Fas-FasL-mediated CD4+ T-cell apoptosis following stem cell transplantation Cancer Res 1999 59: 3107–3111

    CAS  PubMed  Google Scholar 

  6. Cayeux S, Meuer S, Pezzutto A et al. Allogeneic mixed lymphocyte reactions during a second round of ontogeny: normal accessory cells did not restore defective interleukin-2 (IL-2) synthesis in T cells but induced responsiveness to exogeneous IL-2 Blood 1989 74: 2278–2284

    CAS  PubMed  Google Scholar 

  7. Hart D . Dendritic cells: unique leukocyte populations which control the primary immune response Blood 1997 90: 3245–3287

    CAS  PubMed  Google Scholar 

  8. Banchereau J, Steinman R . Dendritic cells and the control of immunity Nature 1998 392: 245–252

    Article  CAS  Google Scholar 

  9. O'Doherty U, Peng M, Gezelter S et al. Human blood contains two subsets of dendritic cells, one immunologically mature and the other immature Immunology 1994 82: 487–493

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Thomas R, Lipsky P . Human peripheral blood dendritic cell subsets J Immun 1994 153: 4016–4028

    CAS  PubMed  Google Scholar 

  11. Takamizawa M, Rivas A, Fagnoni F et al. Dendritic cells that process and present nominal antigens to naive T lymphocytes are derived from CD2+ precursors J Immunol 1997 158: 2134-2142

    Google Scholar 

  12. Kohrgruber N, Halanek N, Groger M et al. Survival, maturation and function of CD11c− and CD11c+ peripheral blood dendritic cells are differentially regulated by cytokines J Immunol 1999 163: 3250–3259

    CAS  PubMed  Google Scholar 

  13. Robinson SP, Patterson S, English N et al. Human peripheral blood contains two distinct lineages of dendritic cells Eur J Immunol 1999 29: 2769–2778

    Article  CAS  Google Scholar 

  14. Rissoan MC, Soumelis V, Kadowaki N et al. Reciprocal control of T helper cell and dendritic cell diferentiation Science 1999 283: 1183–1186

    Article  CAS  Google Scholar 

  15. Siegal FP, Kadowaki N, Shodell M et al. The nature of the principal type 1 interferon-producing cells in human blood Science 1999 284: 1835–1837

    Article  CAS  Google Scholar 

  16. Savary C, Grazziutti M, Melichar B et al. Multidimensional flow-cytometric analysis of dendritic cells in peripheral blood of normal donors and cancer patients Cancer Immunol Immunother 1998 45: 234–240

    Article  CAS  Google Scholar 

  17. Fearnley DB, Whyte LF, Carnoutsos SA et al. Monitoring human blood dendritic cell numbers in normal individuals and in stem cell transplantation Blood 1999 93: 728–736

    CAS  PubMed  Google Scholar 

  18. Mapara M, Korner I, Hildebrandt M et al. Monitoring of tumor cell purging after highly efficient immunmagnetic selection of CD34 cells from leukapheresis products in breast cancer patients: comaprison of immunocytochemical tumor cell staining and reverse transcriptase-polymerase chain reaction Blood 1997 89: 337–344

    CAS  PubMed  Google Scholar 

  19. Dreger P, Viehmann K, von Neuhoff N et al. Autografting of highly purified peripheral blood progenitor cells following myeloablative therapy in patients with lymphoma: a prospective study of the long-term effects on tumor eradication, reconstitution of hematopoiesis and immune recovery Bone Marrow Transplant 1999 24: 153–161

    Article  CAS  Google Scholar 

  20. Klein J, Rey PM, Dansey R et al. Cyclophosphamide and paclitaxel as initial or salvage regimen for the mobilization of peripheral blood progenitor cells Bone Marrow Transplant 1999 24: 959–963

    Article  CAS  Google Scholar 

  21. Peters WP, Shpall EJ, Jones RB et al. High-dose combination alkylating agents with bone marrow support as initial treatment for metastatic breast cancer J Clin Oncol 1988 6: 1368–1376

    Article  CAS  Google Scholar 

  22. Zhou LJ, Tedder TF . CD14+ monocytes can differentiate into functionally mature CD83+ dendritic cells Proc Nat Acad Sci USA 1996 93: 2588–2592

    Article  CAS  Google Scholar 

  23. Sorg R, Kogler G, Wernet P . Identification of cord blood dendritic cells as an immature CD11c- population Blood 1999 93: 2302–2307

    CAS  PubMed  Google Scholar 

  24. Olweus J, BitMansour A, Warnke R et al. Dendritic cell ontogeny: a human dendritic cell lineage of myeloid origin Proc Nat Acad Sci USA 1997 94: 12551–12556

    Article  CAS  Google Scholar 

  25. Res P, Couwenberg F, Vyth-Dreese F, Spits H . Expression of pTalpha mRNA in a committed dendritic cell precursor in the human thymus Blood 1999 94: 2647–2657

    CAS  PubMed  Google Scholar 

  26. Talmadge J, Reed EC, Kessinger A et al. Immunologic attributes of cytokine mobilized peripheral blood stem cells and recovery following transplantation Bone Marrow Transplant 1996 17: 101–109

    CAS  PubMed  Google Scholar 

  27. Hamann D, Baars PA, Rep M et al. Phenotypic and functional separation of memory and effector human CD8+ T cells J Exp Med 1997 186: 1407–1418

    Article  CAS  Google Scholar 

  28. Roederer M, De Rosa S, Watanabe N et al. Dynamics of fine T-cell subsets during HIV disease and after thymic ablation by mediastinal irradiation Semin Immunol 1997 9: 389–396

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are thankful for technical assistance from Shelly Schendel and for technical support from the Karmanos Cancer Institute Flow Cytometry Core Facility. We also thank Dr Beth Hill at SySTEMix Inc. for gifts of reagents.

Author information

Authors and Affiliations

  1. Stem Cell Transplantation Program, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

    A Galy, S Rudraraju, R Baynes & J Klein

Authors
  1. A Galy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Rudraraju
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R Baynes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Galy, A., Rudraraju, S., Baynes, R. et al. Recovery of lymphocyte and dendritic cell subsets after autologous CD34+ cell transplantation. Bone Marrow Transplant 25, 1249–1255 (2000). https://doi.org/10.1038/sj.bmt.1702454

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1702454

Keywords

This article is cited by

Search

Advanced search

Quick links