CD8(+) minor histocompatibility antigen-specific cytotoxic T lymphocyte clones eliminate human acute myeloid leukemia stem cells.
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| Abstract |
Effective immunotherapy for human leukemia based on infusions of T lymphocytes requires the identification of effector T cells that target the leukemic stem cell. The transplantation of human acute myeloid leukemia into nonobese diabetic/severe combined immune deficient (SCID) mice has identified a rare leukemic progenitor termed the SCID leukemia-initiating cell, which is present in low frequency in the leukemic population and is essential for establishing leukemic hematopoiesis. Thus, this transplant model may be ideally suited to identify effector T cells with antileukemic activity. We report that CD8(+) cytotoxic T lymphocyte (CTL) clones specific for minor histocompatibility antigens inhibit the engraftment of human acute myeloid leukemia cells in nonobese diabetic/SCID mice and demonstrate that this inhibition is mediated by direct CTL recognition of SCID leukemia-initiating cells. These results indicate that CD8(+) minor histocompatibility antigen-specific CTL may be mediators of the graft-versus-leukemia effect associated with allogeneic hematopoietic cell transplantation and provide an experimental model to identify and select T cell clones for immunotherapy to prevent or treat relapse after allogeneic hematopoietic cell transplantation.
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| Authors | D Bonnet, E H Warren, P D Greenberg, J E Dick, S R Riddell |
| Journal | Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 96 Issue 15 Pg. 8639-44 (Jul 20 1999) ISSN: 0027-8424 [Print] United States |
| PMID | 10411928 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
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