Direct recognition and lysis of leukemia cells by WT1-specific CD4+ T lymphocytes in an HLA class II-restricted manner.
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.
Guo
Yun
Y
First Department of Internal Medicine, Ehime University School of Medicine, Toon, Ehime 791-0295, Japan.
Niiya
Hironari
H
Azuma
Taichi
T
Uchida
Naoyuki
N
Yakushijin
Yoshihiro
Y
Sakai
Ikuya
I
Hato
Takaaki
T
Takahashi
Masuhiro
M
Senju
Satoru
S
Nishimura
Yasuharu
Y
Yasukawa
Masaki
M
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*
D006682:HLA-DP Antigens; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D025721:WT1 Proteins