International Immunology Advance Access originally published online on February 21, 2005
International Immunology 2005 17(4):421-427; doi:10.1093/intimm/dxh221
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CD25+CD4+ regulatory T cells exert in vitro suppressive activity independent of CTLA-4
1 Department of Molecular Genetics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
2 Department of Medicine II, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, Sapporo 060-8638, Japan
3 Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan
Correspondence to: T. Saito; E-mail: saito{at}rcai.riken.jp
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is constitutively expressed on CD25+CD4+ regulatory T cells (Treg) and is suggested to play a role in Treg-mediated suppression. However, the results of analysis with anti-CTLA-4 have been controversial. We addressed this issue by analyzing mice over-expressing or deficient in CTLA-4. For over-expression, CTLA-4 transgenic mice expressing a full-length (FL) or a truncated (TL) mutant of CTLA-4 were analyzed. FL T cells expressed similar levels of CTLA-4 to Treg, whereas TL T cells expressed much higher levels on the cell surface. The number of Treg in both mice was decreased, although Foxp3 expression was not altered. Treg from both mice exerted suppressive activity, whereas CD25– T cells from FL mice showed no suppression. Furthermore, CD25+CD4 thymocytes from young CTLA-4-deficient mice were analyzed and found to exhibit suppressive activity. These results indicate that Treg exert in vitro suppressive activity independent of CTLA-4 expression.
Keywords: co-stimulation, Foxp3, homeostasis, thymocyte, tolerance
Transmitting editor: S. Koyasu
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