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Depletion of alloreactive T cells via CD69: implications on antiviral, antileukemic and immunoregulatory T lymphocytes

Bone Marrow Transplantation volume 37, pages 297–305 (2006)Cite this article

Abstract

Selective depletion of alloreactive T cells from stem-cell allografts should abrogate graft-versus-host disease while preserving beneficial T cell specificities to facilitate engraftment and immune reconstitution. We therefore explored a refined immunomagnetic separation strategy to effectively deplete alloreactive donor lymphocytes expressing the activation antigen CD69 upon stimulation, and examined the retainment of antiviral, antileukemic, and immunoregulatory T cells. In addition to the CD69high T cell fraction, our studies retrieved two T cell subsets based on residual CD69 expression. Whereas, truly CD69neg cells were devoid of detectable alloresponses to original stimulators, CD69-low (CD69low)-expressing T cells elicited significant residual alloreactivity upon restimulation. In interferon-γ enzyme linked immunospot assays, anti-cytomegalovirus and anti-Epstein–Barr virus responses were preserved at significant numbers among CD69neg T lymphocytes. Accordingly, T cells recognizing the leukemia-associated Wilm's tumor-1 antigen were still detectable in the CD69neg subset. However, antiviral and antileukemic specificities were also consistently found within CD69low T cells, suggesting that memory-type donor T cells were partially captured due to residual CD69 expression. Finally, CD4+CD25+ Foxp3+ immunoregulatory T cells did not upregulate CD69 upon allogeneic stimulation. Our data suggest that CD69-mediated removal of alloreactivity can result in efficient allodepletion, but may partially affect the persistence of antiviral and antileukemic donor memory specificities captured among CD69low-expressing lymphocytes.

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Acknowledgements

This work was supported by grants from the German Cancer Aid (Deutsche Krebshilfe; Projects 70-3344-IIA and IVB), and by a grant from the MAIFOR program of Mainz University School of Medicine.

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  1. U F Hartwig and M Nonn: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine III – Hematology and Oncology, Johannes Gutenberg-University School of Medicine, Mainz, Germany

    U F Hartwig, M Nonn, S Khan, R G Meyer, C Huber & W Herr

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  1. U F Hartwig
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  3. S Khan
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  4. R G Meyer
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Correspondence to U F Hartwig.

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Hartwig, U., Nonn, M., Khan, S. et al. Depletion of alloreactive T cells via CD69: implications on antiviral, antileukemic and immunoregulatory T lymphocytes. Bone Marrow Transplant 37, 297–305 (2006). https://doi.org/10.1038/sj.bmt.1705238

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