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Dendritic Cells Stimulate the Expansion of bcr-abl Specific
CD8+ T Cells With Cytotoxic Activity Against Leukemic
Cells From Patients With Chronic Myeloid Leukemia
Mie Nieda,
Andrew Nicol,
Akiko Kikuchi,
Koichi Kashiwase,
Kerry Taylor,
Kenji Suzuki,
Kenji Tadokoro, and
Takeo Juji
From the Japanese Red Cross Central Blood Center, Tokyo, Japan; the
Department of Hematology, Royal Brisbane Hospital, Brisbane, Australia;
the Department of Hematology, Mater Hospital, Brisbane, Australia; and
the Department of Hematology, The Japanese Red Cross Hospital, Tokyo,
Japan.
The role of T lymphocytes in the control of chronic myeloid leukemia
(CML) after bone marrow transplantations has been clearly shown. This
effect closely correlates with graft-versus-host disease (GVHD). A
specific graft-versus-leukemia (GVL) effect separate from GVHD has been
postulated but has been difficult to show. One possible target for
specific GVL activity is the bcr-abl fusion protein characteristic of
CML. We have investigated the use of normal peptide-pulsed dendritic
cells for the generation of cytotoxic, bcr-abl-specific T cells from
normal donors. T cells (CD3+, CD8+,
TCR  +, and NK receptor-negative) generated from a
normal donor (HLA A24, B52, B59, Cw1) after stimulation with autologous
dendritic cells, primed with a 16 mer peptide spanning the b3a2
breakpoint of bcr-abl, lysed CML cells from the peripheral blood of
seven patients with CML with the b3a2 breakpoint. CML cells from four patients with only the b2a2 breakpoint were not lysed.
Phytohemagglutinin (PHA) blasts derived from peripheral blood of
patients with CML were not lysed, suggesting that cytotoxicity was not
due to alloreactivity. Blocking experiments with anti-HLA-A,B,C
indicated that cytotoxicity was dependent on recognition of major
histocompatibility complex (MHC) class I molecules, although
cytotoxicity was not MHC-restricted because not all patients shared HLA
types with the T-cell donor. Specificity for bcr-abl and absence of
alloreactivity was confirmed by the presence of lytic activity against
autologous and allogeneic class I HLA-A matched monocytes pulsed with
the 16 mer bcr-abl fusion peptide, but not against unpulsed monocytes
or monocytes pulsed with other peptides. These results show that
bcr-abl-specific T cells with marked cytotoxic activity against CML
cells can be generated and amplified from normal donor peripheral
blood. Recognition of HLA molecules is essential for cytotoxicity but
strict HLA identity is not required.
Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 977-983
© 1998 by The American Society of Hematology.
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