CD4(-CELL CLONES SPECIFIC FOR BCR-ABL B3A2 FUSION PEPTIDE AUGMENT COLONY FORMATION BY CHRONIC MYELOGENOUS LEUKEMIA-CELLS IN A B3A2-SPECIFICAND HLA-DR-RESTRICTED MANNER() CYTOTOXIC T)

Although it is well known that CD8(+) cytotoxic T lymphocytes (CTLs) p lay an important role in the suppression of cancer cell growth, the si gnificance of CD4(+) CTLs in resistance to cancer is obscure. In an at tempt to elucidate the role of CD4(+) CTLs in immunosurveillance of ch ronic myelogenous leukemia (CMI), we examined the immunologic function s 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. Restric tion elements of these clones were HLA-DRB10901. These CD4(+) T-cell clones exhibited b3a2 peptide-specific and HLA-DRB1''0901-restricted c ytotoxicity and produced interleukin-3 (IL-3), IL-4, IL-10, interferon -gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony -stimulating factor in response to bcr-abr peptide stimulation, indica ting they were Th0 crones. The numbers of HLA-DRB1''0901-positive b3a2 , but not those of b2a2-positive or HLA-DRB10901-negative CML cell co lonies increased when CML cells were cultured with b3a2-specific CD4() CTL clones. These data suggest that bcr-abl-specific CD4(+) CTLs rec ognize CML cells in an antigen-specific and HLA-DR-restricted manner, and that they do not inhibit, but in fact augment, CML cell growth. (C ) 1998 by The American Society of Hematology.