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Vol. 96, Issue 15, 8639-8644, July 20, 1999

Medical Sciences
 CD8+ minor histocompatibility antigen-specific cytotoxic T lymphocyte clones eliminate human acute myeloid leukemia stem cells

Dominique Bonnet*,dagger ,Dagger , Edus H. Warrendagger ,§,, Philip D. Greenberg§, John E. Dick*, and Stanley R. Riddell§

* Programs in Cancer/Blood Research and Developmental Biology, The Hospital for Sick Children, 555 University Avenue, Toronto M5G 1X8, Ontario, Canada; and § Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA 98109

Communicated by E. Donnall Thomas, Fred Hutchinson Cancer Research Center, Seattle, WA, June 1, 1999 (received for review April 14, 1999)

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.

dagger    D.B. and E.H.W. contributed equally to this work.
Dagger    Present address: Coriell Institute for Medical Research, 401 Haddon Avenue, Camden, NJ, 08103.
   To whom reprint requests should be addressed at: Program In Immunology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D3-100, Seattle, WA 98109. e-mail: ehwarren{at}u.washington.edu.

Copyright © 1999 by The National Academy of Sciences  0027-8424/99/968639-6$2.00/0
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