CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia.

Abstract

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.

• Authors: Carmen Scheibenbogen, Anne Letsch, Eckhard Thiel, Alexander Schmittel, Volker Mailaender, Steffi Baerwolf, Dirk Nagorsen, Ulrich Keilholz
• Journal: Blood (Blood) Vol. 100 Issue 6 Pg. 2132-7 (Sep 15 2002) ISSN: 0006-4971 [Print] United States
• PMID: 12200377 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• HLA-A2 Antigen
• WT1 Proteins
• Interferon-gamma
• GZMB protein, human
• Granzymes
• Serine Endopeptidases
• Myeloblastin

Topics

• Acute Disease
• Antigens, Neoplasm (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Case-Control Studies
• Granzymes
• HLA-A2 Antigen (immunology)
• Humans
• Immunophenotyping
• Interferon-gamma (analysis)
• Leukemia, Myeloid (immunology)
• Myeloblastin
• Serine Endopeptidases (analysis, immunology)
• WT1 Proteins (immunology)