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 Blood, 15 September 2007, Vol. 110, No. 6, pp. 1924-1932.
Prepublished online as a Blood First Edition Paper on May 15, 2007; DOI 10.1182/blood-2007-03-076844.

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IMMUNOBIOLOGY

Graft-versus-leukemia effects associated with detectable Wilms tumor-1–specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia

Katayoun Rezvani1, Agnes S. M. Yong1, Bipin N. Savani1, Stephan Mielke1, Keyvan Keyvanfar1, Emma Gostick2, David A. Price2,3, Daniel C. Douek3, and A. John Barrett1

1 Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; 2 Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; 3 Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD

To determine whether the leukemia-associated Wilms tumor antigen (WT1) contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8+ T-cell responses to WT1 in 10 human lymphocyte antigen (HLA)–A*0201–positive ALL patients during the early phase of immune recovery after SCT (days 30-120). Seven of 10 patients had detectable WT1 expression in their peripheral blood (PB) before SCT by quantitative reverse-transcription polymerase chain reaction. Using WT1/HLA-A*0201 tetramers and intracellular interferon-{gamma} (IFN-{gamma}) staining, WT1+ CD8+ T-cell responses after SCT were found only in patients with detectable WT1 expression before SCT (5 of 7 vs. 0 of 3; P < .05). To monitor the kinetics of WT1+ CD8+ T-cell responses and disease regression after SCT, absolute WT1+ CD8+ T-cell numbers and WT1 expression were studied for each time point. The emergence of WT1+ CD8+ T cells was associated with a decrease in WT1 expression, suggesting a WT1-driven GVL effect. Loss of WT1+ CD8+ T-cell responses was associated with reappearance of WT1 transcripts, consistent with a molecular relapse (P < .001). WT1+ CD8+ T cells had a predominantly effector–memory phenotype (CD45RO+ CD27–CD57+) and produced IFN-{gamma}. Our results support the immunogenicity of WT1 after SCT for ALL and highlight the potential for WT1 vaccines to boost GVL after SCT for ALL.


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