Rat mesenchymal stromal cells inhibit T cell proliferation but not cytokine production through inducible nitric oxide synthase

Frontiers in Immunology

Volumn 3, Issue APR, 2012, Pages

  Zinöcker, Severin ^a,b,c   Vaage, John T ^a,b  

^a OSLO UNIVERSITY HOSPITAL   (Norway)

^b UNIVERSITY OF OSLO   (Norway)

^c NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

Cytokines; Immunosuppression; Mesenchymal stem cells; Mixed lymphocyte reaction; Nitric oxide synthase 2; Prostaglandin E2; Rodent; T lymphocyte activation

Indexed keywords

EID: 84866495472     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2012.00062     Document Type: Article

References (64)

1. Aggarwal,S.,and Pittenger,M. F. (2005). Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105, 1815-1822.
2. Beda, N., and Nedospasov, A. (2005). A spectrophotometric assay for nitrate in an excess of nitrite. Nitric Oxide 13, 93-97.
3. Bogdan, C. (2001). Nitric oxide and the immune response. Nat. Immunol. 2, 907-916.
4. Chabannes, D., Hill, M., Merieau, E., Rossignol, J., Brion, R., Soulillou, J. P., Anegon, I., and Cuturi, M. C. (2007). A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood 110, 3691-3694.
5. Crop, M. J., Baan, C. C., Korevaar, S. S., IJzermans, J. N. M., Pescatori, M., Stubbs, A. P., Van IJcken, W. F. J., Dahlke, M. H., Eggenhofer, E., Weimar, W., and Hoogduijn, M. J. (2010). Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells. Clin. Exp. Immunol. 162, 474-486.
6. da Silva Meirelles, L., Chagastelles, P. C., and Nardi, N. B. (2006). Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J. Cell Sci. 119, 2204-2213.
7. Damoiseaux, J., Döpp, E., Calame, W., Chao, D., MacPherson, G., and Dijkstra, C. (1994). Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1. Immunology 83, 140-147.
8. Dazzi, F., and Krampera, M. (2011). Mesenchymal stem cells and autoimmune diseases. Best Pract. Res. Clin. Haematol. 24, 49-57.
9. Deng, W., Thiel, B., Tannenbaum, C. S., Hamilton, T. A., and Stuehr, D. J. (1993). Synergistic cooperation between T cell lymphokines for induction of the nitric oxide synthase gene in murine peritoneal macrophages. J. Immunol. 151, 322-329.
10. Di Ianni,M.,Del Papa,B.,De Ioanni,M., Moretti, L., Bonifacio, E., Cecchini, D., Sportoletti, P., Falzetti, F., and Tabilio, A. (2008). Mesenchymal cells recruit and regulate T regulatory cells. Exp. Hematol. 36,309-318.
11. Di Nicola, M., Carlo-Stella, C., Magni, M., Milanesi, M., Longoni, P. D., Matteucci, P., Grisanti, S., and Gianni, A. M. (2002). Human bone marrow stromal cells suppress Tlymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99, 3838-3843.
12. Djouad, F., Charbonnier, L. M., Bouffi, C., Louis-Plence, P., Bony, C., Apparailly, F., Cantos, C., Jorgensen, C., and Noel, D. (2007). Mesenchymal stem cells inhibit the differentiation of dendritic cells through an interleukin-6-dependent mechanism. Stem Cells 25, 2025-2032.
13. Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., Deans, R., Keating, A., Prockop, D., and Horwitz, E. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8, 315-317.
14. English, K., Ryan, J. M., Tobin, L., Murphy, M. J., Barry, F. P., and Mahon, B. P. (2009). Cell contact, prostaglandin E2 and transforming growth factor beta-1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25high forkhead box P3+ regulatory T cells. Clin. Exp. Immunol. 156, 149-160.
15. Ghannam, S., Pene, J., Torcy-Moquet, G., Jorgensen, C., and Yssel, H. (2010). Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype. J. Immunol. 185, 302-312.
16. Grohmann, U., and Bronte, V. (2010). Control of immune response by amino acid metabolism. Immunol. Rev. 236, 243-264.
17. Harting, MT., Jimenez, F., Pati, S., Baumgartner, J., and Cox, CS. (2008). Immunophenotype characterization of rat mesenchymal stromal cells. Cytotherapy 10, 243-253.
18. Hoogduijn, M. J., Popp, F., Verbeek, R., Masoodi, M., Nicolaou, A., Baan, C., and Dahlke, M. H. (2010). The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy. Int. Immunopharmacol. 10, 1496-1500.
19. In't Anker, P. S., Noort, W. A., Scherjon, S. A., Kleijburg-van der Keur, C., Kruisselbrink, A. B., van Bezooijen, R. L., Beekhuizen, W., Willemze, R., Kanhai, H. H., and Fibbe, W. E. (2003). Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential. Haematologica 88, 845-852.
20. In't Anker, P. S., Scherjon, S. A., Kleijburg-van der Keur, C., de Groot-Swings, G. M. J. S., Claas, F. H. J., Fibbe, W. E., and Kanhai, H. H. H. (2004). Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 22, 1338-1345.
21. Jones, S., Horwood, N., Cope, A., and Dazzi, F. (2007). The antiproliferative effect of mesenchymal stem cells is a fundamental property shared by all stromal cells. J. Immunol. 179, 2824-2831.
22. Joo, S. Y., Cho, K. A., Jung, Y. J., Kim, H. S., Park, S. Y., Choi, Y. B., Hong, K. M., Woo, S. Y., Seoh, J. Y., Cho, S. J., and Ryu, K. H. (2010). Mesenchymal stromal cells inhibit graftversus-host disease of mice in a dosedependent manner. Cytotherapy 12, 361-370.
23. Krampera, M., Cosmi, L., Angeli, R., Pasini, A., Liotta, F., Andreini, A., Santarlasci, V., Mazzinghi, B., Pizzolo, G., Vinante, F., Romagnani, P., Maggi, E., Romagnani, S., and Annunziato, F. (2006). Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 24, 386-398.
24. Krampera, M., Glennie, S., Dyson, J., Scott, D., Laylor, R., Simpson, E., and Dazzi, F. (2003). Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 101, 3722-3729.
25. Le Blanc, K., Frassoni, F., Ball, L., Locatelli, F., Roelofs, H., Lewis, I., Lanino, E., Sundberg, B., Bernardo, M. E., Remberger, M., Dini, G., Egeler, R. M., Bacigalupo, A., Fibbe, W., and Ringdén, O. (2008). Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graftversus-host disease: a phase II study. Lancet 371, 1579-1586.
26. Le Blanc, K., Rasmusson, I., Sundberg, B., Gotherstrom, C., Hassan, M., and Uzunel, M. (2004). Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363, 1439-1441.
27. Le Blanc, K., Tammik, L., Sundberg, B., Haynesworth, S. E., and Ringdén, O. (2003). Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand. J. Immunol. 57, 11-20.
28. Lejeune, P., Lagadec, P., Onier, N., Pinard, D., Ohshima, H., and Jeannin, J. F. (1994). Nitric oxide involvement in tumor-induced immunosuppression. J. Immunol. 152, 5077-5083.
29. Lennon, D. P., and Caplan, A. I. (2006). Isolation of rat marrow-derived mesenchymal stem cells. Exp. Hematol. 34, 1606-1607.
30. Liew, F. Y., Li, Y., Moss, D., Parkinson, C., Rogers, M. V., and Moncada, S. (1991). Resistance to Leishmania major infection correlates with the induction of nitric oxide synthase in murine macrophages. Eur. J. Immunol. 21, 3009-3014.
31. Lorsbach, R. B., Murphy, W. J., Lowenstein, C. J., Snyder, S. H., and Russell, S. W. (1993). Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. Molecular basis for the synergy between interferongamma and lipopolysaccharide. J. Biol. Chem. 268, 1908-1913.
32. Lukacs-Kornek, V., Malhotra, D., Fletcher, A. L., Acton, S. E., Elpek, K. G., Tayalia, P., Collier, A. R., and Turley, S. J. (2011). Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activatedTcellpoolinlymphnodes. Nat. Immunol. 12, 1096-1104.
33. Martin, P. J., Uberti, J. P., Soiffer, R. J., Klingemann, H., Waller, E. K., Daly, A. S., Herrmann, R. P., Kebriaei, P. (2010). Prochymal improves response rates in patients with steroid-refractory acute graft versus host disease (SR-GVHD) involving the liver and gut: results of a randomized, placebo-controlled, multicenter phase III trial in GVHD. Biology of Blood and Marrow Transplantation 16, S169-S170.
34. Medot-Pirenne, M., Heilman, M. J., Saxena, M., McDermott, P. E., and Mills, C. D. (1999). Augmentation of an antitumor CTL response in vivo by inhibition of suppressor macrophage nitric oxide. J. Immunol. 163, 5877-5882.
35. Meisel, R., Zibert, A., Laryea, M., Gobel, U., Daubener, W., and Dilloo, D. (2004). Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3dioxygenase-mediated tryptophan degradation. Blood 103, 4619-4621.
36. Min, C. K., Kim, B. G., Park, G., Cho, B., and Oh, I. H. (2007). IL-10transduced bone marrow mesenchymal stem cells can attenuate the severity of acute graft-versus-host disease after experimental allogeneic stem cell transplantation. Bone Marrow Transplant. 39, 637-645.
37. Mougiakakos, D., Jitschin, R., Johansson, C. C., Okita, R., Kiessling, R., and Le Blanc, K. (2011). The impact of inflammatory licensing on heme oxygenase-1-mediated induction of regulatory T cells by human mesenchymal stem cells. Blood 117, 4826-4835.
38. Muñoz-Fernández, M. A., Fernández, M. A., and Fresno, M. (1992). Synergism between tumor necrosis factor-alpha and interferongamma on macrophage activation for the killing of intracellular Trypanosoma cruzi through a nitric oxide-dependent mechanism. Eur. J. Immunol. 22, 301-307.
39. Najar, M., Rouas, R., Raicevic, G., Boufker, H. I., Lewalle, P., Meuleman, N., Bron, D., Toungouz, M., Martiat, P., and Lagneaux, L. (2009). Mesenchymal stromal cells promote or suppress the proliferation of T lymphocytes from cord blood and peripheral blood: the importance of low cell ratio and role of interleukin6. Cytotherapy 11, 570-583.
40. Nasef, A., Ashammakhi, N., and Fouillard, L. (2008). Immunomodulatory effect of mesenchymal stromal cells: possible mechanisms. Regen. Med. 3, 531-546.
41. Nauta, A. J., and Fibbe, W. E. (2007). Immunomodulatory properties of mesenchymal stromal cells. Blood 110, 3499-3506.
42. Nicklas,W.,Baneux,P.,Boot,R.,Decelle, T., Deeny, A. A., Fumanelli, M., and Illgen-Wilcke, B. (2002). Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. Lab. Anim. 36, 20-42.
43. Niedbala, W., Cai, B., and Liew, F. Y. (2006). Role of nitric oxide in the regulation of T cell functions. Ann. Rheum. Dis. 65, iii37-iii40.
44. Niedbala, W., Cai, B., Liu, H., Pitman, N., Chang, L., and Liew, F. Y. (2007). Nitric oxide induces CD4+CD25+ Foxp3 regulatory T cells from CD4+CD25 T cells via p53, IL2, and OX40. Proc. Natl. Acad. Sci. U.S.A. 104, 15478-15483.
45. Nombela-Arrieta, C., Ritz, J., and Silberstein, L. E. (2011). The elusive nature and function of mesenchymal stem cells. Nat. Rev. Mol. Cell Biol. 12, 126-131.
46. Oh, I., Ozaki, K., Sato, K., Meguro, A., Tatara, R., Hatanaka, K., Nagai, T., Muroi, K., and Ozawa, K. (2007). Interferon-[gamma] and NF-[kappa]B mediate nitric oxide production by mesenchymal stromal cells. Biochem. Biophys. Res. Commun. 355, 956-962.
47. Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., and Marshak, D. R. (1999). Multilineage potential of adult human mesenchymal stem cells. Science 284, 143-147.
48. Polchert, D., Sobinsky, J., Douglas, G., Kidd, M., Moadsiri, A., Reina, E., Genrich, K., Mehrotra, S., Setty, S., Smith, B., and Bartholomew, A. (2008). IFN-γ activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur. J. Immunol. 38, 1745-1755.
49. Ren, G., Su, J., Zhang, L., Zhao, X., Ling, W., L'Huillie, A., Zhang, J., Lu, Y., Roberts, A. I., Ji, W., Zhang, H., Rabson, A. B., and Shi, Y. (2009). Species variation in the mechanisms of mesenchymal stem cell-mediated immunosuppression. Stem Cells 27, 1954-1962.
50. Ren, G., Zhang, L., Zhao, X., Xu, G., Zhang, Y., Roberts, A. I., Zhao, R. C., and Shi, Y. (2008). Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2, 141-150.
51. Renner, P., Eggenhofer, E., Rosenauer, A., Popp, F. C., Steinmann, J. F., Slowik, P., Geissler, E. K., Piso, P., Schlitt, H. J., and Dahlke, M. H. (2009). Mesenchymal stem cells require a sufficient, ongoing immune response to exert their immunosuppressive function. Transplant. Proc. 41, 2607-2611.
52. Ringdén, O., Uzunel, M., Rasmusson, I., Remberger, M., Sundberg, B., Lonnies, H., Marschall, H. U., Dlugosz, A.,Szakos,A.,Hassan,Z.,Omazic,B., Aschan,J.,Barkholt,L.,and Le Blanc, K. (2006). Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 81, 1390-1397.
53. Ryan, J., Barry, F., Murphy, J., and Mahon, B. (2007). Interferon-γ does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin. Exp. Immunol. 149, 353-363.
54. Sato, K., Ozaki, K., Oh, I., Meguro, A., Hatanaka, K., Nagai, T., Muroi, K., and Ozawa, K. (2007). Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood 109, 228-234.
55. Tian, Y., Deng, Y. B., Huang, Y. J., and Wang, Y. (2008). Bone marrowderived mesenchymal stem cells decrease acute graft-versus-host disease after allogeneic hematopoietic stem cells transplantation. Immunol. Invest. 37, 29-42.
56. Tisato, V., Naresh, K., Girdlestone, J., Navarrete, C., and Dazzi, F. (2007). Mesenchymal stem cells of cord blood origin are effective at preventing but not treating graftversus-host disease. Leukemia 21, 1992-1999.
57. Tolar, J., Villeneuve, P., and Keating, A. (2011). Mesenchymal stromal cells for graft-versus-host disease. Hum. Gene Ther. 22, 257-262.
58. Uccelli, A., Moretta, L., and Pistoia, V. (2006). Immunoregulatory function of mesenchymal stem cells. Eur. J. Immunol. 36, 2566-2573.
59. Waterman, R. S., Tomchuck, S. L., Henkle, S. L., and Betancourt, A. M. (2010). A New Mesenchymal Stem Cell (MSC) Paradigm: polarization into a pro-inflammatory MSC1 or an immunosuppressive MSC2 phenotype. PLoS ONE 5, e10088. doi:10.1371/journal.pone.0010088
60. Yanez, R., Lamana, M. L., Garcia-Castro, J., Colmenero, I., Ramirez, M., and Bueren, J. A. (2006). Adipose tissuederived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease. Stem Cells 24, 2582-2591.
61. Yoshimura, H., Muneta, T., Nimura, A., Yokoyama, A., Koga, H., and Sekiya, I. (2007). Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res. 327, 449-462.
62. Zinöcker, S., Sviland, L., Dressel, R., and Rolstad, B. (2011a). Kinetics of lymphocyte reconstitution after allogeneic bone marrow transplantation: markers of graft-versushost disease. J. Leukoc. Biol. 90, 177-187.
63. Zinöcker, S., Wang, M., Gaustad, P., Kvalheim, G., Rolstad, B., and Vaage, J. T. (2011b). Mycoplasma contamination revisited: mesenchymal stromal cells harboring mycoplasma hyorhinis potently inhibit lymphocyte proliferation in vitro. PloS ONE 6, e16005. doi:10.1371/journal.pone.0016005
64. Zuk, P. A., Zhu, M., Mizuno, H., Huang, J., Futrell, J. W., Katz, A. J., Benhaim, P., Lorenz, H. P., and Hedrick, M. H. (2001). Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7, 211-228.