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[Cancer Research 63, 4516-4520, August 1, 2003]
© 2003 American Association for Cancer Research

Immunology

Human CD4+ CD25+ Regulatory T Cells Suppress NKT Cell Functions

Takeshi Azuma1, Tsuyoshi Takahashi, Atsushi Kunisato, Tadaichi Kitamura and Hisamaru Hirai

Departments of Hematology and Oncology [T. A., T. T., A. K., H. H.] and Urology [T. A., T. K.], Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan

CD4+CD25+ regulatory T cells play an important role in peripheral tolerance. These cells have been reported to be capable of suppressing the response of CD4+CD25- T cells in vitro. The depletion of these cells evokes effective immune responses to tumor cells in vivo. In this study, we demonstrate that CD4+CD25+ T cells also suppress all subsets of V{alpha}24+NKT cells (V{alpha}24+CD4-CD8- double negative, V{alpha}24+CD4+, and V{alpha}24+CD8+) in both proliferation and cytokine production [IFN-{gamma}, interleukin-4 (IL-4), IL-13, and IL-10]. This suppression is mediated by cell-to-cell contact but not by a humoral factor or the inhibition of antigen-presenting cells. Moreover, the cytotoxic activity of V{alpha}24+NKT cells against some tumor cell lines is suppressed by CD4+CD25+ T cells. This finding is important in developing an effective immunotherapy for cancer.




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