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:

Graft-Versus-Leukaemia

Human γδ+ T lymphocytes have in vitro graft vs leukemia activity in the absence of an allogeneic response

Abstract

Refractory acute lymphoblastic leukemia (ALL) is often incurable, and relapse rates following allogeneic bone marrow transplantation (BMT) remain high. We have reported that patients who develop increased numbers of γδ+ T cells soon after BMT are significantly less likely to relapse. We now show in seven donor/recipient pairs that donor-derived Vδ1+CD4CD8γδ+ T cells are activated and proliferate in response to recipient primary ALL blasts. In addition, these cells have been shown to bind and lyse the recipient ALL blasts. Separately, γδ+ T cells proliferate poorly or not at all in mixed lymphocyte culture against HLA-mismatched unrelated stimulator cells. These observations suggest that allogeneic γδ+ T cells could be an effective immunotherapeutic strategy against refractory disease without the risk of graft-versus-host disease. Bone Marrow Transplantation (2001) 27, 601–606.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Horowitz M, Gale R, Sondel PM et al. Graft versus leukemia reactions after bone marrow transplantation Blood 1990 75: 555–562

    CAS  PubMed  Google Scholar 

  2. Henslee PJ, Thompson JS, Romond EH et al. T cell depletion of HLA and haploidentical marrow reduces graft-versus-host disease but it may impair a graft-versus-leukemia effect Transplant Proc 1987 19: 2071–2073

    Google Scholar 

  3. Sykes M, Romick ML, Sachs DH . Interleukin 2 prevents graft-versus-host disease while preserving the graft-versus-leukemia effect of allogeneic T cells Proc Natl Acad Sci USA 1990 87: 5633–5637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Truitt RL, Atasoylu AA . Contribution of CD4+ and CD8+ T cells to graft-versus-host disease and the graft-versus-leukemia reactivity after transplantation of MHC compatible bone marrow Bone Marrow Transplant 1991 8: 51–58

    CAS  PubMed  Google Scholar 

  5. Weiss L, Lubin I, Factorowich I et al. Effective graft-versus-leukemia effects independent of graft-versus-host disease after T cell depleted allogeneic bone marrow transplantation in a murine model of B cell leukemia/lymphoma J Immunol 1994 153: 2562–2567

    CAS  PubMed  Google Scholar 

  6. Henslee-Downey PJ, Abhyankar SH, Parrish RS et al. Use of partially mismatched related donors extends access to allogeneic marrow transplant Blood 1997 89: 3864–3872

    CAS  PubMed  Google Scholar 

  7. Esslin A, Formby B . Comparison of cytolytic and proliferative activities of human γδ and αβ T-cells from peripheral blood against various human tumor cell lines J Natl Cancer Inst 1994 83: 1564–1568

    Article  Google Scholar 

  8. Duval M, Yotnda P, Bensussan A et al. Potential antileukemic effect of gamma delta T cells in acute lymphoblastic leukemia Leukemia 1995 9: 863–868

    CAS  PubMed  Google Scholar 

  9. Lamb LS, Henslee-Downey PJ, Parrish RS et al. Increased frequency of TCR-γδ+ T-cells in disease-free survivors following T-cell depleted partially mismatched bone marrow transplantation for leukemia J Hematother 1996 5: 503–509

    Article  PubMed  Google Scholar 

  10. Lamb LS, Gee A, Hazlett L et al. Influence of T cell depletion method on circulating γδ+ T cell reconstitution and potential role in the graft-versus-leukemia effect Cytotherapy 1999 1: 7–19

    Article  PubMed  Google Scholar 

  11. Antin JH . Graft-versus-leukemia: no longer an epiphenomenon Blood 1993 82: 2273–2277

    CAS  PubMed  Google Scholar 

  12. Barrett AJ . Strategies to enhance the graft-versus-malignancy effect in allogeneic transplants Ann NY Acad Sci 1996 XX: 203–212

    Google Scholar 

  13. Truitt RL, Johnson BD . Principles of graft-versus-leukemia reactivity Biol Blood Marrow Transplant 1995 1: 61–68

    CAS  PubMed  Google Scholar 

  14. Datta AR, Barrett AJ, Jiang YZ et al. Distinct T cell populations distinguish chronic myeloid leukemia cells from lymphocytes in the same individual: a model for separating GVHD from GVL reactions Bone Marrow Transplant 1994 14: 517–524

    CAS  PubMed  Google Scholar 

  15. Champlin R . Separation of graft-versus-host disease and graft-versus-leukemia effect against chronic myelogenous leukemia Exp Hematol 1995 23: 1148–1151

    CAS  PubMed  Google Scholar 

  16. Steinle A, Groh V, Spies T . Diversification, expression, and gamma delta T cell recognition of evolutionarily distinct members of the MIC family of major histocompatibility complex class I-related molecules Proc Natl Acad Sci USA 1998 95: 12510–12515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fisch P, Malkovska M, Braakman E et al. Gamma/delta T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility-restricted cytolysis J Exp Med 1990 171: 1567–1579

    Article  CAS  PubMed  Google Scholar 

  18. Kaur I, Voss SD, Gupta RS et al. Human peripheral gamma/delta T cells recognize hsp60 molecules on Daudi Burkitt's lymphoma cells J Immunol 1993 150: 2046–2055

    CAS  PubMed  Google Scholar 

  19. Battistini L, Salvetti M, Falcone B et al. Gamma delta T cell receptor analysis supports a role for HSP 70 selection of lymphocytes in multiple sclerosis lesions Mol Med 1995 1: 554–562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chouaib F, Porto P, Delorme D et al. Further evidence for a γ/δ T cell receptor-mediated TCT.1/CD48 recognition J Immunol 1991 147: 2864–2867

    Google Scholar 

  21. Hacker G, Kromer S, Falk M et al. Vδ1+ subset of human γδ T cells responds to ligands expressed by EBV-infected Burkitt lymphoma cells and transformed B lymphocytes J Immunol 1992 149: 3984–3989

    CAS  PubMed  Google Scholar 

  22. Marx S, Wesch D, Kabelitz D . Activation of human γδ T cells by Mycobacterium tuberculosis and Daudi lymphoma cells J Immunol 1997 158: 2842–2848

    CAS  PubMed  Google Scholar 

  23. Melenhorst J, van Luxemberg-Heijs S, Landegent J et al. Aplastic anemia in donor cells 14 years after bone-marrow transplant Lancet 1999 353: 2037–2038

    Article  CAS  PubMed  Google Scholar 

  24. Norton J, AI-Saffar N, Sloane JP . An immunohistological study of γδ lymphocytes in human cutaneous graft-versus-host disease Bone Marrow Transplant 1991 7: 205–208

    CAS  PubMed  Google Scholar 

  25. Tsuji S, Char S, Bucy R et al. γδ T cells are secondary participants in acute graft-versus-host interactions initiated by CD4+ αβ T cells Eur J Immunol 1996 26: 420–427

    Article  CAS  PubMed  Google Scholar 

  26. Viale M, Ferrini S, Bacigalupo A . TCR γ/δ positive lymphocytes after allogeneic bone marrow transplantation Bone Marrow Transplant 1992 10: 249–253

    CAS  PubMed  Google Scholar 

  27. Cela ME, Holiday MS, Rooney CM et al. γδ+ T-lymphocyte regeneration after T- lymphocyte-depleted bone marrow transplantation from mismatched family members or matched unrelated donors Bone Marrow Transplant 1996 17: 243–247

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Kerry Bridges and the clinical research staff for their important role in patient identification and accrual and Dr KY Chiang for his review and commentary on the manuscript. We also thank Dr Thomas Spies and Dr Veronica Groh for performing MICA and MICB immunophenotyping.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lamb, L., Musk, P., Ye, Z. et al. Human γδ+ T lymphocytes have in vitro graft vs leukemia activity in the absence of an allogeneic response. Bone Marrow Transplant 27, 601–606 (2001). https://doi.org/10.1038/sj.bmt.1702830

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1702830

Keywords

This article is cited by

Search

Quick links