Identification of FOXP3-negative regulatory T-like (CD4(+)CD25(+)CD127(low)) cells in patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome |
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| Authors: | Otsubo Keisuke Kanegane Hirokazu Kamachi Yoshiro Kobayashi Ichiro Tsuge Ikuya Imaizumi Masue Sasahara Yoji Hayakawa Akira Nozu Kandai Iijima Kazumoto Ito Shuichi Horikawa Reiko Nagai Yoshinori Takatsu Kiyoshi Mori Hisashi Ochs Hans D Miyawaki Toshio |
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| Affiliation: | aDepartment of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan;bDepartment of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan;cDepartment of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan;dDepartment of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan;eDepartment of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan;fDepartment of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan;gDepartment of Hematology and Oncology, Miyagi Children's Hospital, Sendai, Japan;hDepartment of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan;iDepartment of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan;jDepartment of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan;kDepartment of Endocrinology, National Center for Child Health and Development, Tokyo, Japan;lToyama Prefectural Institute for Pharmaceutical Research, Toyama, Japan;mDepartment of Pediatrics, University of Washington School of Medicine and Seattle Children's Research Institute, Seattle, USA |
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| Abstract: | Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an autoimmune disorder caused by mutations in the FOXP3 gene, which plays a key role in the generation of CD4+CD25+regulatory T (Treg) cells. We selected CD127 as the surface marker of Treg cells to illustrate the development and function of Treg cells in IPEX syndrome. CD4+CD25+FOXP3+ T cells, the putative Treg cells, were almost completely absent in all patients. Importantly, a substantial number of CD4+CD25+CD127low T cells were observed in 3 IPEX patients with hypomorphic mutations in the FOXP3 gene. We demonstrated that CD4+CD25+CD127low T cells isolated from these 3 patients exhibited an appreciable suppressive activity on effector T cell proliferation, although less than that displayed by Treg cells from healthy controls. These results suggest that genetically altered FOXP3 can drive the generation of functionally immature Treg cells, but that intact FOXP3 is necessary for the complete function of Treg cells. |
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| Keywords: | Abbreviations: APC, antigen-presenting cells FKH, forkhead FOXP3, forkhead box protein 3 HSCT, hematopoietic stem cell transplantation mAb, monoclonal antibodies MLR, mixed lymphocyte reaction IPEX, immune dysregulation, polyendocrinopathy, enteropathy, X-linked PBMC, peripheral blood mononuclear cell Treg, regulatory T |
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