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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1415-1418.
Prepublished online as a Blood First Edition Paper on April 21, 2005; DOI 10.1182/blood-2005-01-0413.
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Submitted January 31, 2005
Accepted April 12, 2005
Direct recognition and lysis of leukemia cells by WT1-specific CD4+ T lymphocytes in an HLA class II-restricted manner
Yun Guo, Hironari Niiya, Taichi Azuma, Naoyuki Uchida, Yoshihiro Yakushijin, Ikuya Sakai, Takaaki Hato, Masuhiro Takahashi, Satoru Senju, Yasuharu Nishimura, and Masaki Yasukawa*
First Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan
School of Health Sciences, Faculty of Medicine, Niigata University, Niigata, Japan
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
* Corresponding author; email: yasukawa{at}m.ehime-u.ac.jp.
WT1 has been recognized as an attractive target antigen of immunotherapy for various malignancies including leukemia. Since tumor-associated antigen-specific CD4+ T lymphocytes undoubtedly play an important role in the induction of an anti-tumor immune response, we attempted to generate WT1-specific CD4+ T lymphocytes in vitro and examined their anti-leukemia 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, WT1337-347 LSHLQMHSRKH, in an HLA-DP5-restriced 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.

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