Muhaimin Rifa'i, Zhe Shi, Shu-Yun Zhang, Young Ho Lee, Hiroshi Shiku, Ken-Ichi Isobe, Haruhiko Suzuki
CD8+CD122+ regulatory T cells (CD8+ CD122+ Treg) are naturally occurring Treg that effectively suppress the proliferation and IFN-γ 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-γ production from the target T cells. CD8+CD122+ Treg effectively suppressed the IFN-γ 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, αβTCR 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 - αβTCR and become active regulatory cells that produce IL-10 and suppress the target cells. © The Japanese Society for Immunology. 2008. All rights reserved.
Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Department of Biology, Faculty of Science, Brawijaya University, Malang 65145 East-Java, Indonesia; Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Department of Cancer Vaccine, Mie University Graduate School of Medicine, Tsu 514-8507, Japan; Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, Tsu 514-8507, Japan
