title: 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.
abstract: 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(+) 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(+) T cells when co-cultured with them. Moreover, CD8(+) 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(+) T cell function, as evaluated by proliferation and cytokine production. In addition, the production of prostaglandin E2 (PGE2 ), indoleamine 2, 3-dioxygenase (IDO) and transforming growth factor (TGF)-β1 were increased when BMSCs were co-cultured with CD8(+) T cells. The addition of specific inhibitors against PGE2 , IDO and TGF-β partially restored the proliferation of CD8(+) T cells. Our results suggest that BMSCs suppress CD8(+) T cell-mediated activation by suppressing NKG2D expression and secretion of PGE2, 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-versus-host disease (GVHD).
authors: Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, China; Clinical Laboratory, First Affiliated Hospital of the University of Chinese Medicine in Guangxi, Nanning, China.
authors: Mingfen
authors: M
authors: Li
authors: Xuyong
authors: X
authors: Sun
authors: Xiaocong
authors: X
authors: Kuang
authors: Yan
authors: Y
authors: Liao
authors: Haibin
authors: H
authors: Li
authors: Dianzhong
authors: D
authors: Luo
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D053804:Granzymes / Q000096:biosynthesis; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D015395:Histocompatibility Antigens Class I; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007376:Interleukin-2; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D053804:Granzymes; D015232:Dinoprostone
keywords: CD8+ T lymphocytes; NKG2D; immunosuppression; mesenchymal stem cell; soluble factor