Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Chemokine and chemokine receptor expression analysis in target organs of acute graft-versus-host disease

Genes & Immunity volume 10, pages 687–701 (2009)Cite this article

Abstract

Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic bone marrow transplantation (allo-BMT), and infiltration of donor leukocytes into aGVHD target organs is partially orchestrated by chemokines. Using a murine BMT model, the expression of 30 chemokines or chemokine receptors in the lung, liver, gut and tongue was analyzed using real-time PCR at 1, 2, 3 and 6 weeks after BMT during the development of clinical aGVHD and target organ histopathology. CXCL9–11 expression was linked to elevated expression of CXCR3 in the gut, lung and tongue. In contrast, hepatic CXCR3 expression was not changed, whereas a clear association was seen for CXCL16 and CXCR6 expression. An elevated intestinal CCL3 expression 1 week after allo-BMT was associated with an increased expression of CCR5 but not CCR1 or CCR3, and in the lung and liver CCL3–CCL5 expression was associated with increases in CCR1 and CCR5. Overexpression of CCL2, CCL8, CCL12 and their receptor CCR2 was found in the liver and lung, but not in the gut and tongue. On the basis of the differences in kinetics and organ distribution, more studies are required to better characterize specific targets within this network, as this will allow the development of novel preventive and therapeutic approaches by using single or multiple targeting reagents.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Armitage JO . Bone marrow transplantation. N Engl J Med 1994; 330: 827–838.

    Article  CAS  PubMed  Google Scholar 

  2. Goker H, Haznedaroglu IC, Chao NJ . Acute graft-vs-host disease: pathobiology and management. Exp Hematol 2001; 29: 259–277.

    Article  CAS  PubMed  Google Scholar 

  3. Murphy PM, Baggiolini M, Charo IF, Hebert CA, Horuk R, Matsushima K et al. International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev 2000; 52: 145–176.

    CAS  PubMed  Google Scholar 

  4. Murphy PM . International Union of Pharmacology. XXX. Update on chemokine receptor nomenclature. Pharmacol Rev 2002; 54: 227–229.

    Article  CAS  PubMed  Google Scholar 

  5. Zlotnik A, Yoshie O . Chemokines: a new classification system and their role in immunity. Immunity 2000; 12: 121–127.

    Article  CAS  PubMed  Google Scholar 

  6. Rot A, von Andrian UH . Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. Annu Rev Immunol 2004; 22: 891–928.

    Article  CAS  PubMed  Google Scholar 

  7. Mackay CR . Chemokines: immunology's high impact factors. Nat Immunol 2001; 2: 95–101.

    Article  CAS  PubMed  Google Scholar 

  8. Pease JE, Williams TJ . The attraction of chemokines as a target for specific anti-inflammatory therapy. Br J Pharmacol 2006; 147 (Suppl 1): S212–S221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Moser B, Wolf M, Walz A, Loetscher P . Chemokines: multiple levels of leukocyte migration control. Trends Immunol 2004; 25: 75–84.

    Article  CAS  PubMed  Google Scholar 

  10. Rollins BJ . Chemokines. Blood 1997; 90: 909–928.

    Article  CAS  PubMed  Google Scholar 

  11. Choi SW, Hildebrandt GC, Olkiewicz KM, Hanauer DA, Chaudhary MN, Silva IA et al. CCR1/CCL5 (RANTES) receptor–ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation. Blood 2007; 110: 3447–3455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Addison CL, Daniel TO, Burdick MD, Liu H, Ehlert JE, Xue YY et al. The CXC chemokine receptor 2, CXCR2, is the putative receptor for ELR+ CXC chemokine-induced angiogenic activity. J Immunol 2000; 165: 5269–5277.

    Article  CAS  PubMed  Google Scholar 

  13. Strieter RM, Burdick MD, Gomperts BN, Belperio JA, Keane MP . CXC chemokines in angiogenesis. Cytokine Growth Factor Rev 2005; 16: 593–609.

    Article  CAS  PubMed  Google Scholar 

  14. Broxmeyer HE . Chemokines in hematopoiesis. Curr Opin Hematol 2008; 15: 49–58.

    Article  CAS  PubMed  Google Scholar 

  15. Ohl L, Henning G, Krautwald S, Lipp M, Hardtke S, Bernhardt G et al. Cooperating mechanisms of CXCR5 and CCR7 in development and organization of secondary lymphoid organs. J Exp Med 2003; 197: 1199–1204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cyster JG . Chemokines and cell migration in secondary lymphoid organs. Science 1999; 286: 2098–2102.

    Article  CAS  PubMed  Google Scholar 

  17. Muller G, Hopken UE, Lipp M . The impact of CCR7 and CXCR5 on lymphoid organ development and systemic immunity. Immunol Rev 2003; 195: 117–135.

    Article  PubMed  Google Scholar 

  18. Mapara MY, Leng C, Kim YM, Bronson R, Lokshin A, Luster A et al. Expression of chemokines in GVHD target organs is influenced by conditioning and genetic factors and amplified by GVHR. Biol Blood Marrow Transplant 2006; 12: 623–634.

    Article  CAS  PubMed  Google Scholar 

  19. New JY, Li B, Koh WP, Ng HK, Tan SY, Yap EH et al. T cell infiltration and chemokine expression: relevance to the disease localization in murine graft-versus-host disease. Bone Marrow Transplant 2002; 29: 979–986.

    Article  CAS  PubMed  Google Scholar 

  20. Sugerman PB, Faber SB, Willis LM, Petrovic A, Murphy GF, Pappo J et al. Kinetics of gene expression in murine cutaneous graft-versus-host disease. Am J Pathol 2004; 164: 2189–2202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jaksch M, Remberger M, Mattsson J . Increased gene expression of chemokine receptors is correlated with acute graft-versus-host disease after allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11: 280–287.

    Article  CAS  PubMed  Google Scholar 

  22. Duffner U, Lu B, Hildebrandt GC, Teshima T, Williams DL, Reddy P et al. Role of CXCR3-induced donor T-cell migration in acute GVHD. Exp Hematol 2003; 31: 897–902.

    Article  CAS  PubMed  Google Scholar 

  23. Hancock WW, Lu B, Gao W, Csizmadia V, Faia K, King JA et al. Requirement of the chemokine receptor CXCR3 for acute allograft rejection. J Exp Med 2000; 192: 1515–1520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hildebrandt GC, Corrion LA, Olkiewicz KM, Lu B, Lowler K, Duffner UA et al. Blockade of CXCR3 receptor:ligand interactions reduces leukocyte recruitment to the lung and the severity of experimental idiopathic pneumonia syndrome. J Immunol 2004; 173: 2050–2059.

    Article  CAS  PubMed  Google Scholar 

  25. Hildebrandt GC, Duffner UA, Olkiewicz KM, Corrion LA, Willmarth NE, Williams DL et al. A critical role for CCR2/MCP-1 interactions in the development of idiopathic pneumonia syndrome after allogeneic bone marrow transplantation. Blood 2004; 103: 2417–2426.

    Article  CAS  PubMed  Google Scholar 

  26. Hildebrandt GC, Olkiewicz KM, Choi S, Corrion LA, Clouthier SG, Liu C et al. Donor T-cell production of RANTES significantly contributes to the development of idiopathic pneumonia syndrome after allogeneic stem cell transplantation. Blood 2005; 105: 2249–2257.

    Article  CAS  PubMed  Google Scholar 

  27. Hildebrandt GC, Olkiewicz KM, Corrion LA, Chang Y, Clouthier SG, Liu C et al. Donor-derived TNF-alpha regulates pulmonary chemokine expression and the development of idiopathic pneumonia syndrome after allogeneic bone marrow transplantation. Blood 2004; 104: 586–593.

    Article  CAS  PubMed  Google Scholar 

  28. Piper KP, Horlock C, Curnow SJ, Arrazi J, Nicholls S, Mahendra P et al. CXCL10–CXCR3 interactions play an important role in the pathogenesis of acute graft-versus-host disease in the skin following allogeneic stem-cell transplantation. Blood 2007; 110: 3827–3832.

    Article  CAS  PubMed  Google Scholar 

  29. Terwey TH, Kim TD, Kochman AA, Hubbard VM, Lu S, Zakrzewski JL et al. CCR2 is required for CD8-induced graft-versus-host disease. Blood 2005; 106: 3322–3330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Varona R, Cadenas V, Gomez L, Martinez AC, Marquez G . CCR6 regulates CD4+ T-cell-mediated acute graft-versus-host disease responses. Blood 2005; 106: 18–26.

    Article  CAS  PubMed  Google Scholar 

  31. Wysocki CA, Burkett SB, Panoskaltsis-Mortari A, Kirby SL, Luster AD, McKinnon K et al. Differential roles for CCR5 expression on donor T cells during graft-versus-host disease based on pretransplant conditioning. J Immunol 2004; 173: 845–854.

    Article  CAS  PubMed  Google Scholar 

  32. Wysocki CA, Jiang Q, Panoskaltsis-Mortari A, Taylor PA, McKinnon KP, Su L et al. Critical role for CCR5 in the function of donor CD4+CD25+ regulatory T cells during acute graft-versus-host disease. Blood 2005; 106: 3300–3307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wysocki CA, Panoskaltsis-Mortari A, Blazar BR, Serody JS . Leukocyte migration and graft-versus-host disease. Blood 2005; 105: 4191–4199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ewing P, Miklos S, Olkiewicz KM, Muller G, Andreesen R, Holler E et al. Donor CD4+ T-cell production of tumor necrosis factor alpha significantly contributes to the early proinflammatory events of graft-versus-host disease. Exp Hematol 2007; 35: 155–163.

    Article  CAS  PubMed  Google Scholar 

  35. Zhang Y, Louboutin JP, Zhu J, Rivera AJ, Emerson SG . Preterminal host dendritic cells in irradiated mice prime CD8+ T cell-mediated acute graft-versus-host disease. J Clin Invest 2002; 109: 1335–1344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Burman AC, Banovic T, Kuns RD, Clouston AD, Stanley AC, Morris ES et al. IFNgamma differentially controls the development of idiopathic pneumonia syndrome and GVHD of the gastrointestinal tract. Blood 2007; 110: 1064–1072.

    Article  CAS  PubMed  Google Scholar 

  37. Welniak LA, Blazar BR, Anver MR, Wiltrout RH, Murphy WJ . Opposing roles of interferon-gamma on CD4+ T cell-mediated graft-versus-host disease: effects of conditioning. Biol Blood Marrow Transplant 2000; 6: 604–612.

    Article  CAS  PubMed  Google Scholar 

  38. Kim YM, Sachs T, Asavaroengchai W, Bronson R, Sykes M . Graft-versus-host disease can be separated from graft-versus-lymphoma effects by control of lymphocyte trafficking with FTY720. J Clin Invest 2003; 111: 659–669.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Mauermann N, Burian J, von Garnier C, Dirnhofer S, Germano D, Schuett C et al. Interferon-gamma regulates idiopathic pneumonia syndrome, a Th17+CD4+ T-cell-mediated graft-versus-host disease. Am J Respir Crit Care Med 2008; 178: 379–388.

    Article  CAS  PubMed  Google Scholar 

  40. Yang YG, Wang H, Asavaroengchai W, Dey BR . Role of interferon-gamma in GVHD and GVL. Cell Mol Immunol 2005; 2: 323–329.

    CAS  PubMed  Google Scholar 

  41. Farber JM . A macrophage mRNA selectively induced by gamma-interferon encodes a member of the platelet factor 4 family of cytokines. Proc Natl Acad Sci USA 1990; 87: 5238–5242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Vanguri P, Farber JM . Identification of CRG-2. An interferon-inducible mRNA predicted to encode a murine monokine. J Biol Chem 1990; 265: 15049–15057.

    Article  CAS  PubMed  Google Scholar 

  43. Widney DP, Xia YR, Lusis AJ, Smith JB . The murine chemokine CXCL11 (IFN-inducible T cell alpha chemoattractant) is an IFN-gamma- and lipopolysaccharide-inducible glucocorticoid-attenuated response gene expressed in lung and other tissues during endotoxemia. J Immunol 2000; 164: 6322–6331.

    Article  CAS  PubMed  Google Scholar 

  44. Gilliam AC, Whitaker-Menezes D, Korngold R, Murphy GF . Apoptosis is the predominant form of epithelial target cell injury in acute experimental graft-versus-host disease. J Invest Dermatol 1996; 107: 377–383.

    Article  CAS  PubMed  Google Scholar 

  45. Sale GE, Raff RF, Storb R . Stem cell regions in filiform papillae of tongue as targets of graft-versus-host disease. Transplantation 1994; 58: 1273–1275.

    Article  CAS  PubMed  Google Scholar 

  46. Whitaker-Menezes D, Jones SC, Friedman TM, Korngold R, Murphy GF . An epithelial target site in experimental graft-versus-host disease and cytokine-mediated cytotoxicity is defined by cytokeratin 15 expression. Biol Blood Marrow Transplant 2003; 9: 559–570.

    Article  CAS  PubMed  Google Scholar 

  47. Baggiolini M . Chemokines and leukocyte traffic. Nature 1998; 392: 565–568.

    Article  CAS  PubMed  Google Scholar 

  48. Sallusto F, Baggiolini M . Chemokines and leukocyte traffic. Nat Immunol 2008; 9: 949–952.

    Article  CAS  PubMed  Google Scholar 

  49. Flier J, Boorsma DM, van Beek PJ, Nieboer C, Stoof TJ, Willemze R et al. Differential expression of CXCR3 targeting chemokines CXCL10, CXCL9, and CXCL11 in different types of skin inflammation. J Pathol 2001; 194: 398–405.

    Article  CAS  PubMed  Google Scholar 

  50. Serody JS, Burkett SE, Panoskaltsis-Mortari A, Ng-Cashin J, McMahon E, Matsushima GK et al. T-lymphocyte production of macrophage inflammatory protein-1alpha is critical to the recruitment of CD8(+) T cells to the liver, lung, and spleen during graft-versus-host disease. Blood 2000; 96: 2973–2980.

    Article  CAS  PubMed  Google Scholar 

  51. Murai M, Yoneyama H, Ezaki T, Suematsu M, Terashima Y, Harada A et al. Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction. Nat Immunol 2003; 4: 154–160.

    Article  CAS  PubMed  Google Scholar 

  52. Wilbanks A, Zondlo SC, Murphy K, Mak S, Soler D, Langdon P et al. Expression cloning of the STRL33/BONZO/TYMSTRligand reveals elements of CC, CXC, and CX3C chemokines. J Immunol 2001; 166: 5145–5154.

    Article  CAS  PubMed  Google Scholar 

  53. Matloubian M, David A, Engel S, Ryan JE, Cyster JG . A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nat Immunol 2000; 1: 298–304.

    Article  CAS  PubMed  Google Scholar 

  54. Dong H, Toyoda N, Yoneyama H, Kurachi M, Kasahara T, Kobayashi Y et al. Gene expression profile analysis of the mouse liver during bacteria-induced fulminant hepatitis by a cDNA microarray system. Biochem Biophys Res Commun 2002; 298: 675–686.

    Article  CAS  PubMed  Google Scholar 

  55. Kelner GS, Kennedy J, Bacon KB, Kleyensteuber S, Largaespada DA, Jenkins NA et al. Lymphotactin: a cytokine that represents a new class of chemokine. Science 1994; 266: 1395–1399.

    Article  CAS  PubMed  Google Scholar 

  56. Muller S, Dorner B, Korthauer U, Mages HW, D′Apuzzo M, Senger G et al. Cloning of ATAC, an activation-induced, chemokine-related molecule exclusively expressed in CD8+ T lymphocytes. Eur J Immunol 1995; 25: 1744–1748.

    Article  CAS  PubMed  Google Scholar 

  57. Tikhonov I, Kitabwalla M, Wallace M, Malkovsky M, Volkman B, Pauza CD . Staphylococcal superantigens induce lymphotactin production by human CD4+ and CD8+ T cells. Cytokine 2001; 16: 73–78.

    Article  CAS  PubMed  Google Scholar 

  58. Palena C, Arlen P, Zeytin H, Greiner JW, Schlom J, Tsang KY . Enhanced expression of lymphotactin by CD8+ T cells is selectively induced by enhancer agonist peptides of tumor-associated antigens. Cytokine 2003; 24: 128–142.

    Article  CAS  PubMed  Google Scholar 

  59. Hedrick JA, Saylor V, Figueroa D, Mizoue L, Xu Y, Menon S et al. Lymphotactin is produced by NK cells and attracts both NK cells and T cells in vivo. J Immunol 1997; 158: 1533–1540.

    CAS  PubMed  Google Scholar 

  60. Amescua G, Collings F, Sidani A, Bonfield TL, Rodriguez JP, Galor A et al. Effect of CXCL-1/KC production in high risk vascularized corneal allografts on T cell recruitment and graft rejection. Transplantation 2008; 85: 615–625.

    Article  CAS  PubMed  Google Scholar 

  61. Reutershan J, Morris MA, Burcin TL, Smith DF, Chang D, Saprito MS et al. Critical role of endothelial CXCR2 in LPS-induced neutrophil migration into the lung. J Clin Invest 2006; 116: 695–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ichiba T, Teshima T, Kuick R, Misek DE, Liu C, Takada Y et al. Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays. Blood 2003; 102: 763–771.

    Article  CAS  PubMed  Google Scholar 

  63. Zhou L, Askew D, Wu C, Gilliam AC . Cutaneous gene expression by DNA microarray in murine sclerodermatous graft-versus-host disease, a model for human scleroderma. J Invest Dermatol 2007; 127: 281–292.

    Article  CAS  PubMed  Google Scholar 

  64. Luster AD . Chemokines—chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338: 436–445.

    Article  CAS  PubMed  Google Scholar 

  65. Hasegawa H, Inoue A, Kohno M, Lei J, Miyazaki T, Yoshie O et al. Therapeutic effect of CXCR3-expressing regulatory T cells on liver, lung and intestinal damages in a murine acute GVHD model. Gene Therapy 2008; 15: 171–182.

    Article  CAS  PubMed  Google Scholar 

  66. Sato K, Nakaoka T, Yamashita N, Yagita H, Kawasaki H, Morimoto C et al. TRAIL-transduced dendritic cells protect mice from acute graft-versus-host disease and leukemia relapse. J Immunol 2005; 174: 4025–4033.

    Article  CAS  PubMed  Google Scholar 

  67. Ueha S, Murai M, Yoneyama H, Kitabatake M, Imai T, Shimaoka T et al. Intervention of MAdCAM-1 or fractalkine alleviates graft-versus-host reaction associated intestinal injury while preserving graft-versus-tumor effects. J Leukoc Biol 2007; 81: 176–185.

    Article  CAS  PubMed  Google Scholar 

  68. Panoskaltsis-Mortari A, Strieter RM, Hermanson JR, Fegeding KV, Murphy WJ, Farrell CL et al. Induction of monocyte- and T-cell-attracting chemokines in the lung during the generation of idiopathic pneumonia syndrome following allogeneic murine bone marrow transplantation. Blood 2000; 96: 834–839.

    Article  CAS  PubMed  Google Scholar 

  69. Morita NI, Matsumura Y, Morita K, Miyachi Y . Expression of CCR5 in graft-versus-host disease (GVHD) of the skin: immunohistochemical staining of 38 cases. J Dermatol 2007; 34: 254–257.

    Article  PubMed  Google Scholar 

  70. Murai M, Yoneyama H, Harada A, Yi Z, Vestergaard C, Guo B et al. Active participation of CCR5(+)CD8(+) T lymphocytes in the pathogenesis of liver injury in graft-versus-host disease. J Clin Invest 1999; 104: 49–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Dorner BG, Scheffold A, Rolph MS, Huser MB, Kaufmann SH, Radbruch A et al. MIP-1alpha, MIP-1beta, RANTES, and ATAC/lymphotactin function together with IFN-gamma as type 1 cytokines. Proc Natl Acad Sci USA 2002; 99: 6181–6186.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Muller K, Bischof S, Sommer F, Lohoff M, Solbach W, Laskay T . Differential production of macrophage inflammatory protein 1gamma (MIP-1gamma), lymphotactin, and MIP-2 by CD4(+) Th subsets polarized in vitro and in vivo. Infect Immun 2003; 71: 6178–6183.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Nguyen KD, Fohner A, Booker JD, Dong C, Krensky AM, Nadeau KC . XCL1 enhances regulatory activities of CD4+ CD25(high) CD127(low/−) T cells in human allergic asthma. J Immunol 2008; 181: 5386–5395.

    Article  CAS  PubMed  Google Scholar 

  74. Middel P, Thelen P, Blaschke S, Polzien F, Reich K, Blaschke V et al. Expression of the T-cell chemoattractant chemokine lymphotactin in Crohn's disease. Am J Pathol 2001; 159: 1751–1761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Kurt RA, Bauck M, Harma S, McCulloch K, Baher A, Urba WJ . Role of C chemokine lymphotactin in mediating recruitment of antigen-specific CD62L(lo) cells in vitro and in vivo. Cell Immunol 2001; 209: 83–88.

    Article  CAS  PubMed  Google Scholar 

  76. Wang CR, Liu MF, Huang YH, Chen HC . Up-regulation of XCR1 expression in rheumatoid joints. Rheumatology (Oxford) 2004; 43: 569–573.

    Article  CAS  Google Scholar 

  77. Ordway D, Higgins DM, Sanchez-Campillo J, Spencer JS, Henao-Tamayo M, Harton M et al. XCL1 (lymphotactin) chemokine produced by activated CD8T cells during the chronic stage of infection with Mycobacterium tuberculosis negatively affects production of IFN-gamma by CD4T cells and participates in granuloma stability. J Leukoc Biol 2007; 82: 1221–1229.

    Article  CAS  PubMed  Google Scholar 

  78. Streblow DN, Kreklywich C, Yin Q, De La Melena VT, Corless CL, Smith PA et al. Cytomegalovirus-mediated upregulation of chemokine expression correlates with the acceleration of chronic rejection in rat heart transplants. J Virol 2003; 77: 2182–2194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Panoskaltsis-Mortari A, Hermanson JR, Haddad IY, Wangensteen OD, Blazar BR . Intercellular adhesion molecule-I (ICAM-I, CD54) deficiency segregates the unique pathophysiological requirements for generating idiopathic pneumonia syndrome (IPS) versus graft-versus-host disease following allogeneic murine bone marrow transplantation. Biol Blood Marrow Transplant 2001; 7: 368–377.

    Article  CAS  PubMed  Google Scholar 

  80. Matsuyoshi H, Senju S, Hirata S, Yoshitake Y, Uemura Y, Nishimura Y . Enhanced priming of antigen-specific CTLs in vivo by embryonic stem cell-derived dendritic cells expressing chemokine along with antigenic protein: application to antitumor vaccination. J Immunol 2004; 172: 776–786.

    Article  CAS  PubMed  Google Scholar 

  81. Panoskaltsis-Mortari A, Hermanson JR, Taras E, Wangensteen OD, Charo IF, Rollins BJ et al. Post-BMT lung injury occurs independently of the expression of CCL2 or its receptor, CCR2, on host cells. Am J Physiol Lung Cell Mol Physiol 2004; 286: L284–L292.

    Article  CAS  PubMed  Google Scholar 

  82. Rao AR, Quinones MP, Garavito E, Kalkonde Y, Jimenez F, Gibbons C et al. CC chemokine receptor 2 expression in donor cells serves an essential role in graft-versus-host-disease. J Immunol 2003; 171: 4875–4885.

    Article  CAS  PubMed  Google Scholar 

  83. Nikolic B, Lee S, Bronson RT, Grusby MJ, Sykes M . Th1 and Th2 mediate acute graft-versus-host disease, each with distinct end-organ targets. J Clin Invest 2000; 105: 1289–1298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Nonomura A, Kono N, Mizukzmi Y, Nakanuma Y, Matsubara F . Histological changes in the liver in experimental graft-versus-host disease across minor histocompatibility barriers. VI. A light and electron microscopic study of the periportal changes. Liver 1991; 11: 278–286.

    Article  CAS  PubMed  Google Scholar 

  85. Koski GK, Lyakh LA, Cohen PA, Rice NR . CD14+ monocytes as dendritic cell precursors: diverse maturation-inducing pathways lead to common activation of NF-kappab/RelB. Crit Rev Immunol 2001; 21: 179–189.

    Article  CAS  PubMed  Google Scholar 

  86. Ouaaz F, Arron J, Zheng Y, Choi Y, Beg AA . Dendritic cell development and survival require distinct NF-kappaB subunits. Immunity 2002; 16: 257–270.

    Article  CAS  PubMed  Google Scholar 

  87. Buonocore S, Flamand V, Goldman M, Braun MY . Bone marrow-derived immature dendritic cells prime in vivo alloreactive T cells for interleukin-4-dependent rejection of major histocompatibility complex class II antigen-disparate cardiac allograft. Transplantation 2003; 75: 407–413.

    Article  CAS  PubMed  Google Scholar 

  88. Nouri-Shirazi M, Guinet E . Direct and indirect cross-tolerance of alloreactive T cells by dendritic cells retained in the immature stage. Transplantation 2002; 74: 1035–1044.

    Article  CAS  PubMed  Google Scholar 

  89. Cooke KR, Kobzik L, Martin TR, Brewer J, Delmonte Jr J, Crawford JM et al. An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation: I. The roles of minor H antigens and endotoxin. Blood 1996; 88: 3230–3239.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was support by the Deutsche Krebshilfe e.V., Project #106647. We thank the Biostatistician Dr Christoph Ehret (Department of Hematology and Oncology, University of Regensburg Medical Center) for his advice and assistance with the statistical analyses.

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, University of Regensburg Medical School, Regensburg, Germany

    A Bouazzaoui, E Spacenko, G Mueller, S Miklos, E Holler, R Andreesen & G C Hildebrandt

  2. Department of Pathology, University of Regensburg Medical School, Regensburg, Germany

    E Huber

Authors
  1. A Bouazzaoui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E Spacenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G Mueller
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Miklos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E Huber
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E Holler
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R Andreesen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G C Hildebrandt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G C Hildebrandt.

Additional information

Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bouazzaoui, A., Spacenko, E., Mueller, G. et al. Chemokine and chemokine receptor expression analysis in target organs of acute graft-versus-host disease. Genes Immun 10, 687–701 (2009). https://doi.org/10.1038/gene.2009.49

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/gene.2009.49

Keywords

This article is cited by

Search

Advanced search

Quick links