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

Effective immunotherapy for human leukemia based on infusions of T lymphocy tes requires the identification of effector T cells that target the leukemi c stem cell. The transplantation of human acute myeloid leukemia into nonob ese 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 e stablishing leukemic hematopoiesis. Thus, this transplant model may be idea lly suited to identify effector T cells with antileukemic activity. We repo rt that CD8(+) cytotoxic T lymphocyte (CTL) clones specific for minor histo compatibility antigens inhibit the engraftment of human acute myeloid leuke mia cells in nonobese diabetic/SCID mice and demonstrate that this inhibiti on is mediated by direct CTL recognition of SCID leukemia-initiating cells. These results indicate that CD8(+) minor histocompatibility antigen-specif ic 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.