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.

  • Letter to the Editor
  • Published:

B-cell enrichment and infusion in CD4+/CD8+ T-cell depleted products for donor innate immune lymphocyte infusion: is risk of EBV-associated lymphocyte post transplantation lymphoproliferative disease a concern?

Bone Marrow Transplantation volume 41, pages 995–996 (2008)Cite this article

T-lymphocyte therapy for malignant disease has been the focus of a great deal of basic and clinical research for nearly two decades, although much of this work has focused on augmentation of adaptive immunity. Growing evidence suggests that γδ T cells form part of the innate immune defense and are potent antitumor effectors, especially against leukemia,1, 2, 3, 4 lymphoma5, 6 and myeloma.7 Although a number of in vitro and in vivo studies suggest that γδ T cells might be ideally suited for immunotherapeutic applications specifically in the context of hematopoietic stem cell transplantation (HSCT), no studies have specifically addressed the role of γδ T-cell therapy in this setting to date.

Smetak et al.8 have developed a current good manufacturing practice (cGMP) compatible validated method for enriching innate immune effector lymphocytes which should provide clinicians with the means to deliver NK and γδ T-cell therapy. This is a welcome addition to previous methods which relied on soluble anti-αβ monoclonal antibodies and rabbit complement to achieve the same goal.9 Our group validated CD4/CD8 T-cell depletion using similar techniques for a donor innate lymphocyte infusion (DILI) clinical trial intended for prophylaxis against relapse for high-risk acute leukemia in an ongoing pediatric BMT trial (BB IDE 13041). We found that the B-cell content of the graft to be unacceptably high, requiring us to administer large doses of B cells to achieve the γδ and NK doses required by the trial. Table 1 shows the pre- and post-depletion graft composition from one donor. Since our trial requires DILI to be administered 40–60 days following BMT, we were concerned that the infusion of large numbers of B cells to immunosuppressed patients soon following transplant could place some patients at risk for EBV-associated post transplant lymphoproliferative disease (PTLD). We therefore will be adding a step to deplete B cells using CD19-coated ferromagnetic microspheres (Miltenyi, Auburn, CA, USA) before initiating patient accrual.

Table 1 Percents and counts of leukocytes expressing various lineage markers in the apheresis products before and after CliniMACS selections
Full size table

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

References

  1. Duval M, Yotnda P, Bensussan A, Oudhiri N, Guidal C, Rohrlich P et al. Potential antileukemic effect of gamma delta T cells in acute lymphoblastic leukemia. Leukemia 1995; 9: 863–868.

    CAS  PubMed  Google Scholar 

  2. Lamb Jr LS, Musk P, Ye Z, van Rhee F, Geier SS, Tong JJ et al. Human gammadelta(+) T lymphocytes have in vitro graft vs leukemia activity in the absence of an allogeneic response. Bone Marrow Transplant 2001; 27: 601–606.

    Article  Google Scholar 

  3. Hacker G, Kromer S, Falk M, Heeg K, Wagner H, Pfeffer K . V delta 1+ subset of human gamma delta 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 

  4. Dolstra H, Fredrix H, van der Meer A, de Witte T, Figdor C, van de Wiel-van Kemenade E . TCR gamma delta cytotoxic T lymphocytes expressing the killer cell-inhibitory receptor p58.2 (CD158b) selectively lyse acute myeloid leukemia cells. Bone Marrow Transplant 2001; 27: 1087–1093.

    Article  CAS  Google Scholar 

  5. Catellani S, Poggi A, Bruzzone A, Dadati P, Ravetti JL, Gobbi M et al. Expansion of Vdelta1 T lymphocytes producing IL-4 in low-grade non-Hodgkin lymphomas expressing UL-16-binding proteins. Blood 2007; 109: 2078–2085.

    Article  CAS  Google Scholar 

  6. Wilhelm M, Kunzmann V, Eckstein S, Reimer P, Weissinger F, Ruediger T et al. Gammadelta T cells for immune therapy of patients with lymphoid malignancies. Blood 2003; 102: 200–206.

    Article  CAS  Google Scholar 

  7. Kunzmann V, Bauer E, Feurle J, Weissinger F, Tony HP, Wilhelm M . Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Blood 2000; 96: 384–392.

    CAS  PubMed  Google Scholar 

  8. Smetak M, Kimmel B, Birkmann J, Schaefer-Eckart K, Einsele H, Wilhelm M et al. Clinical-scale single-step CD4(+) and CD8(+) cell depletion for donor innate lymphocyte infusion (DILI). Bone Marrow Transplant 2007 (e-pub ahead of print: 26 November 2007).

  9. Marciniak E, Henslee-Downey PJ, Bailey K, Thompson J (eds). Bone Marrow Purging of T-lymphocytes with T10B9 Monoclonal Antibodies and Complement. FA Davis Co: Philadelphia, 1992.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Bone Marrow Transplantation and Cellular Therapy Program, University of Alabama School of Medicine, Birmingham, AL, USA

    L S Lamb Jr

  2. Department of Pediatrics, Bone Marrow Transplantation and Cellular Therapy Program, University of Alabama School of Medicine, Birmingham, AL, USA

    L S Lamb Jr & J Sande

Authors
  1. L S Lamb Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Sande
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L S Lamb Jr.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lamb, L., Sande, J. B-cell enrichment and infusion in CD4+/CD8+ T-cell depleted products for donor innate immune lymphocyte infusion: is risk of EBV-associated lymphocyte post transplantation lymphoproliferative disease a concern?. Bone Marrow Transplant 41, 995–996 (2008). https://doi.org/10.1038/bmt.2008.17

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2008.17

Search

Advanced search

Quick links