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Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3355-3361
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
Masaki Yasukawa,
Hideki Ohminami,
Shin Kaneko,
Yoshihiro Yakushijin,
Yasuharu Nishimura,
Koiti Inokuchi,
Tsuyoshi Miyakuni,
Shinji Nakao,
Kenji Kishi,
Ichiro Kubonishi,
Kazuo Dan, and
Shigeru Fujita
From the First Department of Internal Medicine, Ehime University
School of Medicine, Ehime; the Division of Immunogenetics, Department
of Neuroscience and Immunology, Kumamoto University Graduate School of
Medical Sciences, Kumamoto; the Division of Hematology, Third
Department of Internal Medicine, Nippon Medical School, Tokyo; the
Department of Internal Medicine, Okinawa Prefectural Hospital, Okinawa;
the Third Department of Internal Medicine, Kanazawa University School
of Medicine, Ishikawa; the First Department of Internal Medicine,
Niigata University School of Medicine, Niigata; and the Third
Department of Internal Medicine, Kochi Medical School, Kochi, Japan.
Although 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- , tumor necrosis factor- , 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.
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