Dendritic Cells Stimulate the Expansion of bcr-abl Specific CD8+ T Cells With Cytotoxic Activity Against Leukemic Cells From Patients With Chronic Myeloid Leukemia

摘要: The role of T lymphocytes in the control 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) separate from GVHD postulated but difficult to show. One possible target for GVL activity is bcr-abl fusion protein characteristic CML. We have investigated use normal peptide-pulsed dendritic cells generation cytotoxic, bcr-abl–specific donors. (CD3+, CD8+, TCRαβ+, and NK receptor-negative) generated a donor (HLA A24, B52, B59, Cw1) stimulation autologous cells, primed 16 mer peptide spanning b3a2 breakpoint bcr-abl, lysed CML peripheral blood seven patients breakpoint. four only b2a2 were not lysed. Phytohemagglutinin (PHA) blasts derived lysed, suggesting that cytotoxicity was due alloreactivity. Blocking experiments anti–HLA-A,B,C indicated dependent on recognition major histocompatibility complex (MHC) class I molecules, although MHC-restricted because all shared HLA types T-cell donor. Specificity absence alloreactivity confirmed by presence lytic against allogeneic HLA-A matched monocytes pulsed peptide, unpulsed or other peptides. These results show marked cytotoxic can be amplified blood. Recognition molecules essential strict identity required.