Identification of FOXP3-negative regulatory T-like (CD4(+)CD25(+)CD127(low)) cells in patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2011-10, Vol.141 (1), p.111-120
• Main 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
• Format: Article
• Language: English
• Subjects: Adult; Case-Control Studies; Cell Differentiation - genetics; Cell Differentiation - immunology; Child; Child, Preschool; Female; Forkhead Transcription Factors - deficiency; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - immunology; Genetic Diseases, X-Linked - genetics; Genetic Diseases, X-Linked - immunology; Genetic Diseases, X-Linked - therapy; Hematopoietic Stem Cell Transplantation; Humans; Interleukin-7 Receptor alpha Subunit - metabolism; Male; Mutation; Polyendocrinopathies, Autoimmune - genetics; Polyendocrinopathies, Autoimmune - immunology; Polyendocrinopathies, Autoimmune - therapy; Syndrome; T-Lymphocytes, Regulatory - classification; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology; Young Adult
• ISSN: 1521-7035
• DOI: 10.1016/j.clim.2011.06.006

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(+)CD127(low) T cells were observed in 3 IPEX patients with hypomorphic mutations in the FOXP3 gene. We demonstrated that CD4(+)CD25(+)CD127(low) 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.