Skip to main content
Article thumbnail
Location of Repository

CD200 Positive Human Mesenchymal Stem Cells Suppress TNF-Alpha Secretion from CD200 Receptor Positive Macrophage-Like Cells

By Mika Pietilä, Siri Lehtonen, Elina Tuovinen, Kaarina Lähteenmäki, Saara Laitinen, Hannu-Ville Leskelä, Antti Nätynki, Juha Pesälä, Katrina Nordström and Petri Lehenkari


Human mesenchymal stem cells (hMSCs) display immunosuppressive properties in vitro and the potential has also been transferred successfully to clinical trials for treatment of autoimmune diseases. OX-2 (CD200), a member of the immunoglobulin superfamily, is widely expressed in several tissues and has recently been found from hMSCs. The CD200 receptor (CD200R) occurs only in myeloid-lineage cells. The CD200-CD200R is involved in down-regulation of several immune cells, especially macrophages. The present study on 20 hMSC lines shows that the CD200 expression pattern varied from high (CD200Hi) to medium (CD200Me) and low (CD200Lo) in bone marrow-derived mesenchymal stem cell (BMMSC) lines, whereas umbilical cord blood derived mesenchymal stem cells (UCBMSCs) were constantly negative for CD200. The role of the CD200-CD200R axis in BMMSCs mediated immunosuppression was studied using THP-1 human macrophages. Interestingly, hMSCs showed greater inhibition of TNF-α secretion in co-cultures with IFN-γ primed THP-1 macrophages when compared to LPS activated cells. The ability of CD200Hi BMMSCs to suppress TNF-α secretion from IFN-γ stimulated THP-1 macrophages was significantly greater when compared to CD200Lo whereas UCBMSCs did not significantly reduce TNF-α secretion. The interference of CD200 binding to the CD200R by anti-CD200 antibody weakened the capability of BMMSCs to inhibit TNF-α secretion from IFN-γ activated THP-1 macrophages. This study clearly demonstrated that the efficiency of BMMSCs to suppress TNF-α secretion of THP-1 macrophages was dependent on the type of stimulus. Moreover, the CD200-CD200r axis could have a previously unidentified role in the BMMSC mediated immunosuppression

Topics: Research Article
Publisher: Public Library of Science
OAI identifier:
Provided by: PubMed Central

Suggested articles


  1. (1997). Innate immunity: The virtues of a nonclonal system of recognition.
  2. (1997). Innate immunity: Impact on the adaptive immune response.
  3. (2008). Exploring the full spectrum of macrophage activation.
  4. (2008). Resolution-phase macrophages possess a unique inflammatory phenotype that is controlled by cAMP.
  5. (1995). Role of interferon-gamma in immune cell regulation.
  6. (2004). Increased Th1 activity in patients with coronary artery disease.
  7. (2010). Proinflammatory cytokines underlying the inflammation of crohn’s disease.
  8. (2006). Inflammatory bowel disease requires the interplay between innate and adaptive immune signals.
  9. (2005). Interferon-gamma and atherosclerosis: Pro- or anti-atherogenic?
  10. (2010). Proteome bioprofiles distinguish between M1 priming and activation states in human macrophages.
  11. (2005). Human mesenchymal stem cells modulate allogeneic immune cell responses.
  12. (2005). Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells.
  13. (2003). Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex.
  14. (2005). Immunomodulatory effect of human adipose tissue-derived adult stem cells: Comparison with bone marrow mesenchymal stem cells.
  15. (2009). The immunomodulatory activity of human umbilical cord blood-derived mesenchymal stem cells in vitro.
  16. (2010). Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal crohn’s disease: Results of a phase I study.
  17. (2009). Adiposederived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses.
  18. (2008). Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: A phase II study.
  19. (2010). Mesenchymal stem cells prevent acute rejection and prolong graft function in pancreatic islet transplantation.
  20. (2009). Tolllike receptor engagement enhances the immunosuppressive properties of human bone marrow-derived mesenchymal stem cells by inducing indoleamine-2,3-dioxygenase-1 via interferon-beta and protein kinase R.
  21. (2007). Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells.
  22. (2010). Galectin-1 and semaphorin-3A are two soluble factors conferring T-cell immunosuppression to bone marrow mesenchymal stem cell.
  23. (2010). Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression.
  24. (2009). A decreased positivity for CD90 on human mesenchymal stromal cells (MSCs) is associated with a loss of immunosuppressive activity by MSCs.
  25. (1986). Neuronal/lymphoid membrane glycoprotein MRC OX-2 is a member of the immunoglobulin superfamily with a light-chain-like structure.
  26. (1987). Characterization of the human homolog of the rat MRC OX-2 membrane glycoprotein.
  27. (2008). Specific plasma membrane protein phenotype of culture-amplified and native human bone marrow mesenchymal stem cells.
  28. (2000). Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function.
  29. (2000). Downregulation of the macrophage lineage through interaction with OX2 (CD200).
  30. (2008). A critical function for CD200 in lung immune homeostasis and the severity of influenza infection.
  31. (2007). CD200 ligand receptor interaction modulates microglial activation in vivo and in vitro: A role for IL-4.
  32. (2011). Involvement of the CD200 receptor complex in microglia activation in experimental glaucoma. Exp Eye Res.
  33. (2002). Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis.
  34. (2002). Anti-CD200R ameliorates collagen-induced arthritis in mice.
  35. (2001). CD200 immunoadhesin suppresses collagen-induced arthritis in mice.
  36. (2005). CD 200-mediated regulation of skin immunity.
  37. (2010). Human gingiva-derived mesenchymal stem cells elicit polarization of m2 macrophages and enhance cutaneous wound healing.
  38. (2009). Mesenchymal stem cell-educated macrophages: A novel type of alternatively activated macrophages.
  39. (2003). Osteoblast recruitment from stem cells does not decrease by age at late adulthood.
  40. (2011). The isolation and culture of human cord blood-derived mesenchymal stem cells under low oxygen conditions.
  41. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. the international society for cellular therapy position statement.
  42. (2010). Mouse bone marrow-derived mesenchymal stromal cells turn activated macrophages into a regulatory-like profile.
  43. (1993). Phorbol myristate acetatedifferentiated THP-1 cells display increased levels of MHC class I and class II mRNA and interferon-gamma-inducible tumoricidal activity.
  44. (2007). Human placenta promotes IL-8 expression through activation of JNK/SAPK and transcription factors NF-kappaB and AP-1 in PMA-differentiated THP-1 cells.
  45. (1996). Differences in the state of differentiation of THP-1 cells induced by phorbol ester and 1,25-dihydroxyvitamin D3.
  46. (2011). Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche.
  47. (2011). Trumpp A
  48. (2007). CD200 and its receptor, CD200R, modulate bone mass via the differentiation of osteoclasts.
  49. (2011). Tumor necrosis factor alpha promotes the expression of immunosuppressive proteins and enhances the cell growth in a human bone marrow-derived stem cell culture.
  50. (2011). Interferon-gamma regulates the proliferation and differentiation of mesenchymal stem cells via activation of indoleamine 2,3 dioxygenase (IDO).
  51. (2006). Regulation of myeloid cell function through the CD200 receptor.
  52. (2006). Rhesus rhadinovirus R15 encodes a functional homologue of human CD200.
  53. (2009). vOX2 glycoprotein of human herpesvirus 8 modulates human primary macrophages activity.
  54. (2010). The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages.
  55. (2010). CD200R1 regulates the severity of arthritis but has minimal impact on the adaptive immune response.
  56. (2008). CD200-fc, a novel antiarthritic biologic agent that targets proinflammatory cytokine expression in the joints of mice with collagen-induced arthritis.
  57. (2008). Cancer stem cells, CD200 and immunoevasion.
  58. (2007). Coexpression of the toleragenic glycoprotein, CD200, with markers for cancer stem cells.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.