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Chronic Lymphocytic Leukemia, Normal T and B cells (CLL)

Evidence for involvement of clonally expanded CD8+ T cells in anticancer immune responses in CLL patients following nonmyeloablative conditioning and hematopoietic cell transplantation

Leukemia volume 19, pages 2273–2280 (2005)Cite this article

Abstract

We have analyzed the clonotype composition of CD8+ T cells following nonmyeloablative (NMA) conditioning and hematopoietic cell transplantation (HCT), of patients with chronic lymphocytic leukemia (CLL). Consecutive analyses of blood samples taken up to 2 years following HCT, demonstrated that CD8+ T-cell clonality was highly dynamic in the early phases after HCT, but became more stable after 4–5 months. Moreover, donor lymphocyte infusion (DLI) given for disease progression in one of the patients led to establishment of recurrent as well as new T-cell clonotypes. This coincided with disease remission, strongly suggesting that these T cells were engaged with anti-CLL cytotoxicity. To examine the functional capacity of stable clonally expanded T cells after HCT, CD8+ T cells isolated post-transplant from the recipients were stimulated ex vivo with CLL cells and subsequently analyzed by FACS for surface expression of the marker for cytotoxic activity, CD107a. Stimulation with CLL cells indeed led to surface expression of CD107a, and clonotype analyses of sorted cells demonstrated that CD107a positive T cells were stably expanded following HCT. Our data suggest that clonally expanded CD8+ T-cell clones participate in the ongoing T-cell response against CLL cells following HCT with NMA conditioning.

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Acknowledgements

Supported by the Danish Cancer Society, the Novo Nordisk Foundation, Vilhelm Petersen og Hustrus legat by recommendation by the Novo Foundation, Danish Medical Research Council, and the Danish Foundation for Cancer Research.

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Authors and Affiliations

  1. Tumor Immunology Group, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark

    T Kollgaard, S Reker Hadrup, T Seremet, M H Andersen & P thor Straten

  2. Department of Hematology, The Lymphocyte Research Laboratory, Rigshospitalet, Copenhagen, Denmark

    S L Petersen, T N Masmas & L Vindeløv

  3. The Tissue Typing Laboratory, Rigshospitalet, Copenhagen, Denmark

    H O Madsen

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Kollgaard, T., Petersen, S., Hadrup, S. et al. Evidence for involvement of clonally expanded CD8+ T cells in anticancer immune responses in CLL patients following nonmyeloablative conditioning and hematopoietic cell transplantation. Leukemia 19, 2273–2280 (2005). https://doi.org/10.1038/sj.leu.2403972

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