title: Direct recognition and lysis of leukemia cells by WT1-specific CD4+ T lymphocytes in an HLA class II-restricted manner.
abstract: Wilms tumor gene 1 product (WT1) has been recognized as an attractive target antigen of immunotherapy for various malignancies including leukemia. Because tumor-associated antigen-specific CD4+ T lymphocytes undoubtedly play an important role in the induction of an antitumor immune response, we attempted to generate WT1-specific CD4+ T lymphocytes in vitro and examined their antileukemia functions. A CD4+ T-cell line, designated NIK-1, which proliferated and produced Th1 cytokines specifically in response to stimulation with the WT1-derived peptide, WT1(337-347) LSHLQMHSRKH, in an HLA-DP5-restricted manner was established. NIK-1 exhibited cytotoxicity against HLA-DP5-positive, WT1-expressing leukemia cells but did not lyse HLA-DP5-negative, WT1-expressing leukemia cells or HLA-DP5-positive, WT1-negative cells. NIK-1 did not inhibit colony formation by normal bone marrow cells of HLA-DP5-positive individuals. This is the first report to describe WT1-specific and HLA class II-restricted CD4+ T lymphocytes possessing direct cytotoxic activity against leukemia cells.
authors.affiliation: First Department of Internal Medicine, Ehime University School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Yun
authors.initials: Y
authors.lastname: Guo
authors.forename: Hironari
authors.initials: H
authors.lastname: Niiya
authors.forename: Taichi
authors.initials: T
authors.lastname: Azuma
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Uchida
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yakushijin
authors.forename: Ikuya
authors.initials: I
authors.lastname: Sakai
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hato
authors.forename: Masuhiro
authors.initials: M
authors.lastname: Takahashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
mesh_terms: D000595:Amino Acid Sequence; D001854:Bone Marrow Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D006682:HLA-DP Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007938:Leukemia / Q000276:immunology / Q000473:pathology*; D010446:Peptide Fragments / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D025721:WT1 Proteins / Q000276:immunology*
chemical_list: D006682:HLA-DP Antigens; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D025721:WT1 Proteins