Mesenchymal stem cells suppress CD8+ T cell‐mediated activation by suppressing natural killer group 2, member D protein receptor expression and secretion of prostaglandin E2, indoleamine 2, 3‐dioxygenase and transforming growth factor‐β. (December 2014)

• Record Type: Journal Article
• Authors: Li, Mingfen; Sun, Xuyong; Kuang, Xiaocong; Liao, Yan; Li, Haibin; Luo, Dianzhong
• Is Part Of: Clinical and experimental immunology. Volume 178:Number 3(2014:Dec.)
• Page Start: 516
• Page End: 524
• Publication Date: 2014-12
• Subjects: Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12423
• Languages: English
• ISSNs: 0009-9104

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Bone marrow mesenchymal stem cells (BMSCs) inhibit immune cell responsiveness, and especially of T lymphocytes. We showed that BMSCs markedly inhibited the proliferation and cytokine production by CD8<sup>+</sup> T cells by a cell‐to‐cell contact phenomenon and secretion of soluble factors. BMSCs down‐regulate the expression of natural killer group 2, member D protein (NKG2D) receptors on CD8<sup>+</sup> T cells when co‐cultured with them. Moreover, CD8<sup>+</sup> T cells that express low levels of NKG2D had impaired proliferation after triggering by a mitogen. The major histocompatibility complex (MHC) class I chain‐related (MIC) A/B molecule, which is a typical ligand for NKG2D, was expressed on BMSCs, and caused dampening of cell proliferation. Monoclonal antibody blocking experiments targeted to MIC A/B impaired CD8<sup>+</sup> T cell function, as evaluated by proliferation and cytokine production. In addition, the production of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), indoleamine 2, 3‐dioxygenase (IDO) and transforming growth factor (TGF)‐β1 were increased when BMSCs were co‐cultured with CD8<sup>+</sup> T cells. The addition of specific inhibitors against PGE<sub>2</sub>, IDO and TGF‐β partially restored the proliferation of CD8<sup>+</sup> T cells. Our results suggest that BMSCs suppress CD8<sup>+</sup> T cell‐mediated activation by suppressing NKG2D expression and secretion of PGE<sub>2</sub>, IDO and TGF‐β. Our observations further confirm the feasibility of BMSCs as a potential adoptive cellular therapy in immune‐mediated diseases such as graft‐<italic>versus</italic>‐host disease (GVHD).</p> </abstract>