title: Umbilical Cord Tissue-Derived Mesenchymal Stem Cells Induce T Lymphocyte Apoptosis and Cell Cycle Arrest by Expression of Indoleamine 2, 3-Dioxygenase.
abstract: It has been reported that human mesenchymal stem cells are able to inhibit T lymphocyte activation; however, the discrepancy among different sources of MSCs is not well documented. In this study, we have compared the MSCs from bone marrow (BM), adipose tissue (AT), placenta (PL), and umbilical cord (UC) to determine which one displayed the most efficient immunosuppressive effects on phytohemagglutinin-induced T cell proliferation. Among them we found that hUC-MSC has the strongest effects on inhibiting T cell proliferation and is chosen to do the further study. We observed that T lymphocyte spontaneously released abundant IFN-γ. And IFN-γ secreted by T lymphocyte could induce the expression of indoleamine 2, 3-dioxygenase (IDO) in hUC-MSCs. IDO was previously reported to induce T lymphocyte apoptosis and cell cycle arrest in S phase. When cocultured with hUC-MSCs, T lymphocyte expression of caspase 3 was significantly increased, while Bcl2 and CDK4 mRNA expression decreased dramatically. Addition of 1-methyl tryptophan (1-MT), an IDO inhibitor, restored T lymphocyte proliferation, reduced apoptosis, and induced resumption of the cell cycle. In addition, the changes in caspase 3, CDK4, and Bcl2 expression were reversed by 1-MT. These findings demonstrate that hUC-MSCs induce T lymphocyte apoptosis and cell cycle arrest by expressing abundant IDO and provide an explanation for some of the immunomodulatory effects of MSCs.
authors.affiliation: The Scientific Research Center, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, Jilin 130033, China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Li
authors.affiliation: Rehabilitation Department, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, Jilin 130033, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Xu
authors.affiliation: The Scientific Research Center, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, Jilin 130033, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Bai
authors.affiliation: Shulanshi People's Hospital, Shulan, Jilin 132600, China.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yang
authors.affiliation: Shulanshi People's Hospital, Shulan, Jilin 132600, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Eugenom Inc., 11107 Roselle Street, San Diego, CA 92121, USA.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Research Service, Audie L Murphy Division, South Texas Veterans Health Care System, San Antonio, TX 78229-4404, USA; Department of Comprehensive Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Chen
authors.affiliation: The Scientific Research Center, China-Japan Union Hospital, Jilin University, 126 Xiantai Street, Changchun, Jilin 130033, China.
authors.forename: Yimin
authors.identifier: 0000-0002-5110-0859
authors.initials: Y
authors.lastname: Wang