Functional leukemia-associated antigen-specific memory CD8+ T cells exist in healthy individuals and in patients with chronic myelogenous leukemia before and after stem cell transplantation

DOI PDF 10 Citations
  • Katayoun Rezvani
    From the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; Vaccine Research Center, NIH, Bethesda, MD; and the Nuffield Department of Medicine, Oxford, United Kingdom.
  • Matthias Grube
    From the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; Vaccine Research Center, NIH, Bethesda, MD; and the Nuffield Department of Medicine, Oxford, United Kingdom.
  • Jason M. Brenchley
    From the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; Vaccine Research Center, NIH, Bethesda, MD; and the Nuffield Department of Medicine, Oxford, United Kingdom.
  • Giuseppe Sconocchia
    From the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; Vaccine Research Center, NIH, Bethesda, MD; and the Nuffield Department of Medicine, Oxford, United Kingdom.
  • Hiroshi Fujiwara
    From the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; Vaccine Research Center, NIH, Bethesda, MD; and the Nuffield Department of Medicine, Oxford, United Kingdom.
  • David A. Price
    From the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; Vaccine Research Center, NIH, Bethesda, MD; and the Nuffield Department of Medicine, Oxford, United Kingdom.
  • Emma Gostick
    From the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; Vaccine Research Center, NIH, Bethesda, MD; and the Nuffield Department of Medicine, Oxford, United Kingdom.
  • Ko Yamada
    From the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; Vaccine Research Center, NIH, Bethesda, MD; and the Nuffield Department of Medicine, Oxford, United Kingdom.
  • Jan Melenhorst
    From the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; Vaccine Research Center, NIH, Bethesda, MD; and the Nuffield Department of Medicine, Oxford, United Kingdom.
  • Richard Childs
    From the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; Vaccine Research Center, NIH, Bethesda, MD; and the Nuffield Department of Medicine, Oxford, United Kingdom.
  • Nancy Hensel
    From the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; Vaccine Research Center, NIH, Bethesda, MD; and the Nuffield Department of Medicine, Oxford, United Kingdom.
  • Daniel C. Douek
    From the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; Vaccine Research Center, NIH, Bethesda, MD; and the Nuffield Department of Medicine, Oxford, United Kingdom.
  • A. John Barrett
    From the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; Vaccine Research Center, NIH, Bethesda, MD; and the Nuffield Department of Medicine, Oxford, United Kingdom.

Abstract

<jats:title>Abstract</jats:title><jats:p>Antigens implicated in the graft-versus-leukemia (GVL) effect in chronic myeloid leukemia (CML) include WT1, PR1, and BCR-ABL. To detect very low frequencies of these antigen-specific CD8+ T cells, we used quantitative polymerase chain reaction (qPCR) to measure interferon-γ (IFN-γ) mRNA production by peptide-pulsed CD8+ T cells from HLA-A*0201+ healthy volunteers and from patients with CML before and after allogeneic stem cell transplantation (SCT). Parallel assays using cytomegalovirus (CMV) pp65 tetramers demonstrated the IFN-γ copy number to be linearly related to the frequency of tetramer-binding T cells, sensitive to frequencies of 1 responding CD8+ T cell/100 000 CD8+ T cells. Responses to WT1 and PR1 but not BCR-ABL were detected in 10 of 18 healthy donors. Responses to WT1, PR1, or BCR-ABL were observed in 9 of 14 patients with CML before SCT and 5 of 6 after SCT, often to multiple epitopes. Responses were higher in patients with CML compared with healthy donors and highest after SCT. These antigen-specific CD8+ T cells comprised central memory (CD45RO+CD27+CD57–) and effector memory (CD45RO–CD27–CD57+) T cells. In conclusion, leukemia-reactive CD8+ T cells derive from memory T cells and occur at low frequencies in healthy individuals and at higher frequencies in patients with CML. The increased response in patients after SCT suggests a quantitative explanation for the greater effect of allogeneic SCT.</jats:p>

Journal

  • Blood

    Blood 102 (8), 2892-2900, 2003-10-15

    American Society of Hematology

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