Suppressive effects of vitamin C-treated induced-regulatory T cells on heart allograft rejection under vitamin C-deficient or -sufficient conditions

• Published in: PloS one 2021-02, Vol.16 (2), p.e0246967-e0246967
• Main Authors: Hwang, Ju Hee, Piao, Honglin, Jang, Joon Young, Lee, Sun-Kyung, Han, Dongkyu, Lee, Gwang-Min, Go, Cheolhyeon, Kim, Yejin, Oh, Kwon Ik, Kang, Jae Seung, Yan, Ji-Jing, Yang, Jaeseok
• Format: Article
• Language: English
• Subjects: Anatomy; Animals; Ascorbic acid; Ascorbic Acid - immunology; Ascorbic Acid - therapeutic use; Ascorbic Acid Deficiency - complications; Ascorbic Acid Deficiency - drug therapy; Ascorbic Acid Deficiency - immunology; Biology; Biology and Life Sciences; Biomedical materials; Biomedical research; CD28 antigen; CD3 antigen; CD4 antigen; Cell growth; Cloning; Drinking water; Drug dosages; Editing; Electronic mail; Engineering and Technology; Flow cytometry; Genetic aspects; Graduate schools; Graduate studies; Graft rejection; Graft Rejection - complications; Graft Rejection - drug therapy; Graft Rejection - immunology; Heart; Heart Transplantation; Hospitals; Hypersensitivity; Immunological tolerance; Immunology; Immunoregulation; Interleukin 2; Laboratory animals; Lymphocytes; Lymphocytes T; Maintenance; Medical research; Medical schools; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Physical sciences; Physiological aspects; Protocol (computers); Rejection; Research facilities; Reviews; Self; Supplements; Surgery; T cell receptors; T cells; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Transplantation; Vitamin C; Vitamins - immunology; Vitamins - therapeutic use
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0246967

Foxp3 stability of vitamin C-treated induced-regulatory T cells (V-iTregs) is superior to that of conventional iTregs (C-iTregs). However, the role of V-iTregs in allograft rejection under vitamin C-deficient conditions, such as those seen in humans, remains unclear. We aimed to elucidate the role of vitamin C treatment on generation and maintenance of iTregs from gulo knockout (Gulo-KO) mice as well as wild type (WT) mice, and in vitro and in vivo suppressive effects of V-iTregs on heart allograft rejection in either Gulo-KO or WT recipient mice. Conversion efficiency of iTregs was similar between C- and V-iTregs in both WT and Gulo-KO mice. V-iTregs from WT or Gulo-KO mice showed better in vitro Foxp3 stability than C-iTregs, although there was no difference between WT V-iTregs and Gulo-KO V-iTregs. Furthermore, V-iTregs from WT or Gulo-KO mice suppressed in vitro T cell proliferation better than C-iTregs. Heterotrophic heart transplantation from BALB/c mice to WT or vitamin C-deficient Gulo-KO C57BL/6J mice was performed following adoptive transfer of C- or V-iTregs. V-iTregs as well as C-iTregs prolonged heart allograft survival in WT and Gulo-KO mice. However, there was no difference between the C- and V-iTreg groups. Supplementation of low- or high-dose vitamin C did not induce significant changes in heart allograft survival in Gulo-KO recipients that had received V-iTregs. In conclusion, V-iTregs do not exert better suppressive effects on heart allograft survival than C-iTregs in either WT or vitamin C-deficient recipients.