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Prepublished online as a Blood First Edition Paper on May 24, 2002; DOI 10.1182/blood-2002-01-0163.
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Blood, 15 September 2002, Vol. 100, No. 6, pp. 2132-2137
IMMUNOBIOLOGY
CD8 T-cell responses to Wilms tumor gene product WT1 and
proteinase 3 in patients with acute myeloid leukemia
Carmen Scheibenbogen,
Anne Letsch,
Eckhard Thiel,
Alexander Schmittel,
Volker Mailaender,
Steffi Baerwolf,
Dirk Nagorsen, and
Ulrich Keilholz
From Medizinische Klinik III, Hämatologie,
Onkologie und Transfusionsmedizin, Universitätsklinikum
Benjamin-Franklin, Freie Universität Berlin, Germany.
Wilms tumor gene product WT1 and proteinase 3 are overexpressed
antigens in acute myeloid leukemia (AML), against which cytotoxic T
lymphocytes can be elicited in vitro and in murine models. We performed
this study to investigate whether WT1- and proteinase 3-specific CD8 T
cells spontaneously occur in AML patients. T cells recognizing
HLA-A2.1-binding epitopes from WT1 or proteinase 3 could be detected ex
vivo in 5 of 15 HLA-A2-positive AML patients by interferon-
(IFN- ) ELISPOT assay and flow cytometry for intracellular IFN-
and in 3 additional patients by flow cytometry only. T cells producing
IFN- in response to proteinase 3 were further characterized in one
patient by 4-color flow cytometry, identifying them as CD3+CD8+CD45RA+ CCR7
T cells, resembling cytotoxic effector T cells. In line with this
phenotype, most of the WT1- and proteinase-reactive T cells were
granzyme B+. These results provide for the first time
evidence for spontaneous T-cell reactivity against defined antigens in
AML patients. These data therefore support the immunogenicity of WT1
and proteinase 3 in acute leukemia patients and the potential
usefulness of these antigens for leukemia vaccines.

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