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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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NEOPLASIA
Brief report

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

From the First Department of Internal Medicine, Ehime University School of Medicine, Japan; School of Health Sciences, Faculty of Medicine, Niigata University, Japan; and Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Japan.

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, 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. (Blood. 2005;106: 1415-1418)


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