Immunomodulatory mechanism of human cord blood mesenchymal stem cells in allogeneic T cell responses

• Main Author: 莊喬惠
• Other Authors: Shiu-Huey, Chou
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/25252714890858801135

碩士 === 輔仁大學 === 生命科學系碩士班 === 92 === Mesenchymal stem cells (MSCs) are a rare but unique population in that they have self-renewal and differentiation abilities and are able to replenish a variety of specific cell types. In the previously reported in the literatures, MSCs have been shown to be of low immunogenicity and are theoretically suitable for transplantation. It has further been shown that MSCs, when co-cultured with T-lymphocytes in vitro, inhibited proliferation of allogenic T cells. The purpose of this study is to further exploit the regulatory activities of MSCs in the immune system. Our previous study of the in utero xenogenic transplantation experiments indicated that human MSCs survived in mice and did not induce immunologic rejection of the recipients. It is also noted, according to the experimental results in our laboratory, that MSCs derived from umbilical cord blood (uMSCs) showed stronger inhibitory effects of allogenic T-cells than those derived from bone marrow. Therefore we chose to investigate the immunomodulatory effects of uMSCs in this study. The results revealed that uMSC that inhibited allogenic T cell proliferation in the presence of mitogen phytohemaggutinin (PHA), co-stimulatory factors such as CD3 and CD28, and a secondary allogenic T cells. Besides, flow cytometry results revealed that uMSCs reduced the frequency of T cells that enter into cell cycle but did not induce apoptosis. In transwell co-culture system, it was demonstrated that uMSC secreted soluble factors to block T cells proliferation. Furthermore, RT-PCR and ELISA assays showed that cytokines involved in this inhibitory reaction that were IL-10 and TGF-b. We also found that the addition of anti-IL-10 and TGF-b antibodies could rescue allogeneic T cell proliferation when they were co-cultured with uMSCs. It has also been shown that the expression level of CD28 in T cells reduced, and the expression of CTLA-4, an inhibitory molecule, has been up-regulated. Importantly, the numbers of CD4+, CD8+, CD4+CD25+, CD8+CD25+ T cells were significantly increased after the co-cultured with uMSC. The results of this study suggest that uMSC suppress allogeneic T cell responses via the generation of IL-10 and TGF-b mediated regulatory T cells population (Treg).