CD4+ Cytotoxic T-Cell Clones Specific for bcr-abl b3a2 Fusion Peptide Augment Colony Formation by Chronic Myelogenous Leukemia Cells in a b3a2-Specific and HLA-DR–Restricted Manner

Abstract

AbstractAlthough it is well known that CD8+cytotoxic T lymphocytes (CTLs) play an important role in the suppression of cancer cell growth, the significance of CD4+ CTLs in resistance to cancer is obscure. In an attempt to elucidate the role of CD4+ CTLs in immunosurveillance of chronic myelogenous leukemia (CML), we examined the immunologic functions of bcr-abl b3a2 fusion peptide-specific CD4+ CTL clones. Seven CD4+ T-cell clones that responded to stimulation with b3a2 peptide, but not with b2a2 peptide or physiological counterparts bcr b3b4 and abl 1A-a2 peptides, were established from two healthy individuals. Restriction elements of these clones were HLA-DRB1*0901. These CD4+ T-cell clones exhibited b3a2 peptide-specific and HLA-DRB1*0901-restricted cytotoxicity and produced interleukin-3 (IL-3), IL-4, IL-10, interferon-γ, tumor necrosis factor–α, and granulocyte-macrophage colony-stimulating factor in response to bcr-abl peptide stimulation, indicating they were Th0 clones. The numbers of HLA-DRB1*0901-positive b3a2, but not those of b2a2-positive or HLA-DRB1*0901-negative CML cell colonies increased when CML cells were cultured with b3a2-specific CD4+ CTL clones. These data suggest that bcr-abl–specific CD4+ CTLs recognize CML cells in an antigen-specific and HLA-DR–restricted manner, and that they do not inhibit, but in fact augment, CML cell growth.© 1998 by The American Society of Hematology.