CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia.
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-gamma (IFN-gamma) ELISPOT assay and flow cytometry for intracellular IFN-gamma and in 3 additional patients by flow cytometry only. T cells producing IFN-gamma 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.
Scheibenbogen
Carmen
C
Medizinische Klinik III, Hämatologie, Onkologie und Transfusionsmedizin, Universitätsklinikum Benjamin-Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany.
Letsch
Anne
A
Thiel
Eckhard
E
Schmittel
Alexander
A
Mailaender
Volker
V
Baerwolf
Steffi
S
Nagorsen
Dirk
D
Keilholz
Ulrich
U
D000208:Acute Disease; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D053804:Granzymes; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000032:analysis; D007951:Leukemia, Myeloid / Q000276:immunology*; D053146:Myeloblastin; D012697:Serine Endopeptidases / Q000032:analysis / Q000276:immunology*; D025721:WT1 Proteins / Q000276:immunology*
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D025721:WT1 Proteins; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; D053146:Myeloblastin