International Immunology Advance Access originally published online on May 20, 2008
International Immunology 2008 20(7):937-947; doi:10.1093/intimm/dxn052
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CD8+CD122+ regulatory T cells recognize activated T cells via conventional MHC class I–
βTCR interaction and become IL-10-producing active regulatory cells
1 Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
2 Department of Biology, Faculty of Science, Brawijaya University, Malang 65145, East-Java, Indonesia
3 Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
4 Department of Cancer Vaccine
5 Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, Tsu 514-8507, Japan
Correspondence to: H. Suzuki; E-mail: k46200a{at}nucc.cc.nagoya-u.ac.jp
CD8+CD122+ regulatory T cells (CD8+CD122+ Treg) are naturally occurring Treg that effectively suppress the proliferation and IFN-
production of both CD8+ and CD4+ target cells. This study investigated the molecular mechanisms of the recognition of target cells by CD8+CD122+ Treg using an in vitro culture system that reconstitutes the regulatory action of these cells. Naive CD8+CD122+ Treg co-cultured with pre-activated T cells became active Treg that produced IL-10 and suppressed IFN- production from the target T cells. CD8+CD122+ Treg effectively suppressed the IFN- production of the target cells of syngeneic mouse strains but not of allogeneic mouse strains with incompatible MHC. By using MHC-congeneic mouse strains, MHC-restricted suppression by CD8+CD122+ Treg was further confirmed. The blockade of cell surface molecules either on the Treg or on the target cells by specific blocking antibodies indicated that H-2K, H-2D, 
βTCR and CD8 were involved in the regulatory action but I-A and Qa-1 were not. These results indicate that CD8+CD122+ Treg recognize already-activated T cells via the interaction of conventional MHC class I–βTCR and become active regulatory cells that produce IL-10 and suppress the target cells.
Keywords: in vitro assay, mouse, suppression, Treg
* These authors contributed equally to this work.
Transmitting editor: K. Okumura
Received 4 March 2008, accepted 25 April 2008.
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