Human CD4+ CD25+ regulatory T cells suppress NKT cell functions.
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 Valpha24+NKT cells (Valpha24+CD4-CD8- double negative, Valpha24+CD4+, and Valpha24+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 Valpha24+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.
Azuma
Takeshi
T
Department of Hematology and Oncology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. t-azuma@tc4.so-net.ne.jp
Takahashi
Tsuyoshi
T
Kunisato
Atsushi
A
Kitamura
Tadaichi
T
Hirai
Hisamaru
H
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005699:Galactosylceramides / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000097:blood / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D016207:Cytokines; D005699:Galactosylceramides; D007378:Interleukins; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma