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+CD4−CD8−γδ+ 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
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Horowitz M, Gale R, Sondel PM et al. Graft versus leukemia reactions after bone marrow transplantation Blood 1990 75: 555–562
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
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
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
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
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
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
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
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
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
Antin JH . Graft-versus-leukemia: no longer an epiphenomenon Blood 1993 82: 2273–2277
Barrett AJ . Strategies to enhance the graft-versus-malignancy effect in allogeneic transplants Ann NY Acad Sci 1996 XX: 203–212
Truitt RL, Johnson BD . Principles of graft-versus-leukemia reactivity Biol Blood Marrow Transplant 1995 1: 61–68
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
Champlin R . Separation of graft-versus-host disease and graft-versus-leukemia effect against chronic myelogenous leukemia Exp Hematol 1995 23: 1148–1151
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
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
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
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
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
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
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
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
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
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
Viale M, Ferrini S, Bacigalupo A . TCR γ/δ positive lymphocytes after allogeneic bone marrow transplantation Bone Marrow Transplant 1992 10: 249–253
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
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
Rights 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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1702830
Keywords
This article is cited by
-
Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia
Blood Cancer Journal (2021)
-
Regulatory γδ T cells induced by G-CSF participate in acute graft-versus-host disease regulation in G-CSF-mobilized allogeneic peripheral blood stem cell transplantation
Journal of Translational Medicine (2018)
-
Clinical-scale manufacturing of γδ T cells for protection against infection and disease recurrence following haploidentical peripheral blood stem cell transplantation and cyclophosphamide gvhd prophylaxis
Bone Marrow Transplantation (2018)
-
Modern approaches to HLA-haploidentical blood or marrow transplantation
Nature Reviews Clinical Oncology (2016)
-
Cytotoxic and Regulatory Properties of Circulating Vδ1+ γδ T Cells: A New Player on the Cell Therapy Field?
Molecular Therapy (2014)