Skip to main content

Advertisement

SpringerLink
Log in

Post-Transplant Events

Recovery of Vα24+ NKT cells after hematopoietic stem cell transplantation

  • Original Article
  • Published:
Bone Marrow Transplantation Submit manuscript

Summary:

Human Vα24+ natural killer T (NKT) cells have an invariant T-cell receptor-α chain and are activated in a CD1d-restricted manner. Vα24+ NKT cells are thought to regulate immune responses and to play important roles in the induction of allograft tolerance. In this report, we analyzed the recovery of Vα24+ NKT cells after hematopoietic stem cell transplantation and its correlation with graft-versus-host disease (GVHD). Patients who received a dose-reduced conditioning regimen, antithymocyte globulin- or CAMPATH-1H-containing conditioning regimen were excluded. NKT cells were reconstituted within 1 month after transplantation in peripheral blood stem cell transplantation recipients, while their numbers remained low for more than 1 year in bone marrow transplantation (BMT) recipients. The number of Vα24+ NKT cells in BMT recipients with acute GVHD was lower than that in patients without acute GVHD, and both the CD4+ and CD4− Vα24+ NKT subsets were significantly reduced. With regard to chronic GVHD, BMT recipients with extensive GVHD had significantly fewer Vα24+ NKT cells than other patients. Furthermore, the number of CD4+ Vα24+ NKT cells was also significantly reduced in patients with chronic extensive GVHD. Our results raise the possibility that the number of Vα24+ NKT cells could be related to the development of GVHD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Fujimaki K, Maruta A, Yoshida M et al. Immune reconstitution assessed during five years after allogeneic bone marrow transplantation. Bone Marrow Transplant 2001; 27: 1275–1281.

    Article  CAS  PubMed  Google Scholar 

  2. Storek J, Dawson MA, Storer B et al. Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation. Blood 2001; 97: 3380–3389.

    Article  CAS  PubMed  Google Scholar 

  3. Fowlkes BJ, Kruisbeek AM, Ton-That H et al. A novel population of T cell receptor αβ-bearing thymocytes which predominantly express a single Vβ8 gene family. Nature 1987; 329: 251–254.

    Article  CAS  PubMed  Google Scholar 

  4. Budd RC, Miescher GC, Howe RC et al. Developmentally regulated expression of T cell receptor β chain variable domain is immature thymocytes. J Exp Med 1987; 166: 577–582.

    Article  CAS  PubMed  Google Scholar 

  5. Lantz O, Bendelac A . An invariant T cell receptor α chain is used by a unique subset MHC class I-specific CD4+ and CD4−CD8−T cells in mice and humans. J Exp Med 1994; 180: 1097–1106.

    Article  CAS  PubMed  Google Scholar 

  6. Dellabona P, Padovan E, Casorati G et al. An invariant Vα-JαQ/Vα11 T cell receptor is expressed in all individuals by clonally expanded CD4−CD8− cells. J Exp Med 1994; 180: 1171–1176.

    Article  CAS  PubMed  Google Scholar 

  7. Porcelli S, Gerdes D, Fertig AM, Balk SP . Human T cells expressing an invariant Vα24-JαQ TCRα are CD4− and heterogeneous with respect to TCRβ expression. Hum Immunol 1996; 48: 63–67.

    Article  CAS  PubMed  Google Scholar 

  8. Godfrey DI, Hammond KJL, Poulton LD, Baxter AG . NKT cells: facts, functions and fallacies. Immunol Today 2000; 21: 573–583.

    Article  CAS  PubMed  Google Scholar 

  9. Joyce S . CD1d and natural T cells: how their properties jump-start the immune system. Cell Mol Life Sci 2001; 58: 442–469.

    Article  CAS  PubMed  Google Scholar 

  10. Zeng D, Lewis D, Dejbakhsh-Jones S et al. Bone marrow NK1.1− and NK1.1+ T cells reciprocally regulate acute graft versus host disease. J Exp Med 1999; 189: 1073–1081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Baker J, Verneris MR, Ito M et al. Expansion of cytolytic CD8+ natural killer T cells with limited capacity for graft-versus-host disease induction due to interferon γ production. Blood 2001; 97: 2923–2931.

    Article  CAS  PubMed  Google Scholar 

  12. Thiede C, Florek M, Bornhäuser M et al. Rapid quantification of mixed chimerism using multiplex amplification of short tandem repeat markers and fluorescence detection. Bone Marrow Transplant 1999; 23: 1055–1060.

    Article  CAS  PubMed  Google Scholar 

  13. Takahashi T, Nieda M, Koezuka Y et al. Analysis of human Vα24+CD4+ NKT cells activated by α-galactosylceramide-pulsed monocyte-derived dendritic cells. J Immunol 2000; 164: 4458–4464.

    Article  CAS  PubMed  Google Scholar 

  14. Takahashi T, Chiba S, Nieda M et al. Analysis of human Vα24+CD8+ NKT Cells activated by α-galactosylceramide-pulsed monocyte-derived dendritic cells. J Immunol 2002; 168: 3140–3144.

    Article  CAS  PubMed  Google Scholar 

  15. Karadimitris A, Gadola S, Altamirano M et al. Human CD1d-glycolipid tetramers generated by in vitro oxidative refolding chromatography. Proc Natl Acad Sci USA 2001; 98: 3294–3298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lee PT, Benlagha K, Teyton L, Bendelac A . Distinct functional lineages of human Vα24 natural killer T cells. J Exp Med 2002; 195: 637–641.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Exley MA, Tahir SMA, Cheng O et al. A major fraction of human bone marrow lymphocyte are Th2-like CD1d-reactive T cells that can suppress mixed lymphocyte responses. J Immunol 2001; 167: 5531–5534.

    Article  CAS  PubMed  Google Scholar 

  18. Kim CH, Johnston B, Butcher EC . Trafficking machinery of NKT cells: shared and differential chemokine receptor expression among Vα24+Vβ11+ NKT cell subsets with distinct cytokine-producing capacity. Blood 2002; 100: 11–16.

    Article  CAS  PubMed  Google Scholar 

  19. Sonoda K, Exley M, Snapper S et al. CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged site. J Exp Med 1999; 190: 1215–1225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Seino K, Fukao K, Muramoto K et al. Requirement for natural killer T (NKT) cells in the induction of allograft tolerance. Proc Natl Acad Sci USA 2001; 98: 2577–2581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chargui J, Hase T, Wada S et al. NKT cells as nonspecific immune-regulator inducing tolerance in mouse model transplantation. Transplant Proc 2001; 33: 3833–3834.

    Article  CAS  PubMed  Google Scholar 

  22. Higuchi M, Zeng D, Shizuru J et al. Immune tolerance to combined organ and bone marrow transplants after fractionated lymphoid irradiation involves regulatory NKT cells and clonal deletion. J Immunol 2002; 169: 5564–5570.

    Article  CAS  PubMed  Google Scholar 

  23. Ikehara Y, Yasunami Y, Kodama S et al. CD4+Vα24 natural killer T cells are essential for acceptance of rat islet xenografts in mice. J Clin Invest 2000; 105: 1761–1767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gumperz JE, Miyake S, Yamamura T, Brenner MB . Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. J Exp Med 2002; 195: 625–636.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Teshima T, Ferrara JLM . Understanding the alloresponse: new approaches to graft-versus-host disease prevention. Semin Hematol 2002; 39: 15–22.

    Article  PubMed  Google Scholar 

  26. Ellison CA, Fischer JMM, HayGlass KT, Gartner JG . Murine graft-versus-host disease in an F1-hybrid model using IFN-α gene knockout donors. J Immunol 1998; 161: 631–640.

    CAS  PubMed  Google Scholar 

  27. Allen RD, Staley TA, Sidman CL . Differential cytokine expression in acute and chronic murine graft-versus-host-disease. Eur J Immunol 1993; 23: 333–337.

    Article  CAS  PubMed  Google Scholar 

  28. Brok HPM, Heidt PJ, van der Meide PH et al. Interferon-γ prevents graft-versus-host disease after allogeneic bone marrow transplantation in mice. J Immunol 1993; 151: 6451–6459.

    CAS  PubMed  Google Scholar 

  29. Yang YG, Dey BR, Sergio JJ et al. Donor-derived interferon γ is required for inhibition of acute graft-versus-host disease by interleukin 12. J Clin Invest 1998; 102: 2126–2135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Murphy WJ, Welniak LA, Taub DD et al. Differential effects of the absence of interferon-γ and IL-4 in acute graft-versus-host disease after allogeneic bone marrow transplantation in mice. J Clin Invest 1998; 102: 1742–1748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lan F, Zeng D, Higuchi M et al. Predominance of NK1.1+TCRαβ+ or DX5+TCRαβ+ T cells in mice conditioned with fractionated lymphoid irradiation protects against graft-versus-host disease: ‘natural suppressor’ cells. J Immunol 2001; 167: 2087–2096.

    Article  CAS  PubMed  Google Scholar 

  32. Takahashi T, Nakamura K, Chiba S et al. Vα24+ natural killer T cells are markedly decreased in atopic dermatitis patients. Hum Immunol 2003; 64: 586–592.

    Article  CAS  PubMed  Google Scholar 

  33. Sonoda K, Faunce DE, Taniguchi M et al. NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance. J Immunol 2001; 166: 42–50.

    Article  CAS  PubMed  Google Scholar 

  34. Taylor PA, Lees CJ, Blazar BR . The infusion of ex vivo activated and expanded CD4+CD25+ immune regulatory cells inhibits graft-versus-host disease lethality. Blood 2002; 99: 3493–3499.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Eri Nagata for providing excellent technical assistance.

Author information

Author notes

  1. H Hirai: Hisamaru Hirai died on August 23, 2003, during the preparation of this manuscript.

Authors and Affiliations

  1. Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan

    K Haraguchi, T Takahashi, Y Kanda, S Ogawa, S Chiba & H Hirai

  2. Hematopoietic Cell Transplantation Team, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Tokyo, Japan

    K Haraguchi, K Hiruma, Y Tanaka & H Sakamaki

  3. Department of Hematology and Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan

    K Haraguchi & O Miura

Authors
  1. K Haraguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K Hiruma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Chiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. O Miura
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H Sakamaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. H Hirai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K Haraguchi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Haraguchi, K., Takahashi, T., Hiruma, K. et al. Recovery of Vα24+ NKT cells after hematopoietic stem cell transplantation. Bone Marrow Transplant 34, 595–602 (2004). https://doi.org/10.1038/sj.bmt.1704582

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704582

  • Springer Nature Limited

Keywords

This article is cited by

Search

Navigation