Biology of Blood and Marrow Transplantation
Volume 14, Issue 9 , Pages 973-984 , September 2008

CpG-Induced Myeloid CD11b+Gr-1+ Cells Efficiently Suppress T Cell–Mediated Immunoreactivity and Graft-Versus-Host Disease in a Murine Model of Allogeneic Cell Therapy

  • Shoshana Morecki

      Affiliations

    • Department of Bone Marrow Transplantation, Cancer Immunotherapy & Immunobiology Research Center, Hadassah University Hospital, Jerusalem, Israel
    • Corresponding Author InformationCorrespondence and reprint requests: Shoshana Morecki, PhD, Department of Bone Marrow Transplantation, Cancer Immunotherapy & Immunobiology Research Center, Hadassah University Hospital, Jerusalem 91120, Israel.
    • ,
  • Yael Gelfand

      Affiliations

    • Department of Bone Marrow Transplantation, Cancer Immunotherapy & Immunobiology Research Center, Hadassah University Hospital, Jerusalem, Israel
    • ,
  • Elena Yacovlev

      Affiliations

    • Department of Bone Marrow Transplantation, Cancer Immunotherapy & Immunobiology Research Center, Hadassah University Hospital, Jerusalem, Israel
    • ,
  • Osnat Eizik

      Affiliations

    • Department of Bone Marrow Transplantation, Cancer Immunotherapy & Immunobiology Research Center, Hadassah University Hospital, Jerusalem, Israel
    • ,
  • Yehudit Shabat

      Affiliations

    • Department of Bone Marrow Transplantation, Cancer Immunotherapy & Immunobiology Research Center, Hadassah University Hospital, Jerusalem, Israel
    • ,
  • Shimon Slavin

      Affiliations

    • The International Centre for Cell Therapy and Cancer, Tel Aviv (Souraski) Medical Center, Tel Aviv 64239, Israel

Received 28 April 2008 ,Accepted 30 June 2008.

References 

  1. Krieg AM. CpG motif in bacterial DNA and their immune effect. Annu Rev Immunol. 2002;20:709–760
  2. Vollmer J, Weeratna R, Payette P, et al. Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities. Eur J Immunol. 2004;34:251–262
  3. Krieg AM, Yi AK, Matson S, et al. CpG motif in bacterial DNA trigger direct B-cell activation. Nature. 1995;374:546–549
  4. Roda JM, Parihar R, Carson WE. CpG-containing oligodeoxynucleotides act through TLR9 to enhance the NK cell cytokine response to antibody-coated tumor cells. J Immunol. 2005;175:1619–1627
  5. Sparwasser T, Miethke T, Lipford G, et al. Macrophages sense pathogens via DNA motif: induction of tumor necrosis factor-α–mediated shock. Eur J Immunol. 1997;27:1671–1679
  6. Sparwasser T, Koch ES, Vabulas RM, et al. Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and activation of murine dendritic cells. Eur J Immunol. 1998;28:2045–2054
  7. Kumagai Y, Takeuchi O, Akira S. TLR9 as a key receptor for the recognition of DNA. Adv Drug Deliv Rev. 2008;60:795–804
  8. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol. 2004;5:987–995
  9. Akira S, Takeda K, Kaisho T. Toll-like receptors: critical protein linking innate and acquired immunity. Nat Immunol. 2001;2:675–680
  10. Chu RS, Targoni OS, Krieg AM, et al. CpG oligodeoxynucleotides act as adjuvant that switch on T helper 1 (Th1) immunity. J Exp Med. 1997;186:1623–1631
  11. Weeratna RD, Brazolot Millan CL, McCluskie MJ, et al. CpG ODN can redirect the Th bias of established Th2 immune responses in adult and young mice. FEMS Immunol Med Microbiol. 2001;32:65–71
  12. Stern BV, Boehm BO, Tary-Lehmann M. Vaccination with tumor peptide in CpG adjuvant protect via IFNγ-dependent CD4 cell immunity. J Immunol. 2002;168:6099–6105
  13. Miconnet I, Koenig S, Speiser D, et al. CpG are efficient adjuvants for specific CTL induction against tumor antigen–derived peptide. J Immunol. 2002;168:1212–1218
  14. Mo JH, Park SW, Rhee CS, et al. Suppression of allergic response by CpG motif oligodeoxynucleotide-house-dust mite conjugate in animal model of allergic rhinitis. Am J Rhinol. 2006;20:212–218
  15. Ho PP, Fontoura P, Ruiz PJ, et al. An immunomodulatory CpG oligonucleotide for the treatment of autoimmunity via the innate and adaptive immune system. J Immunol. 2003;171:4920–4926
  16. Kline JN, Waldschmidt TJ, Businga TR, et al. Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma. J Immunol. 1998;160:2555–2559
  17. Horowitz MM, Gale RP, Sondel PM, et al. Graft-versus-leukemia reaction after bone marrow transplantation. Blood. 1990;75:555–562
  18. Slavin S, Naparstek E, Nagler A, et al. Allogeneic cell therapy: the treatment of choice for all hematologic malignancies relapsing post-BMT. Blood. 1996;87:4011–4014
  19. Slavin S. Immunotherapy of cancer with alloreactive lymphocytes. Lancet Oncol. 2001;2:491–498
  20. Cohen P, Vourka-Karussis U, Weiss L, et al. Spontaneous and IL-2–induced anti-leukemic and anti-host effect against tumor- and host-specific alloantigens. J Immunol. 1993;151:4803–4810
  21. Morecki S, Yacovlev E, Diab A, et al. Allogeneic cell therapy for a murine mammary carcinoma. Cancer Res. 1998;58:3891–3895
  22. Small TN, Papadopoulos EB, Boulad F, et al. Comparison of immune reconstitution after unrelated and related T cell-depleted bone marrow transplantation: effect of patients age and donor leukocyte infusion. Blood. 1999;93:467–480
  23. Parkman R, Cohen G, Carter SL, et al. Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation. Biol Blood Marrow Transplant. 2006;12:919–927
  24. Morecki S, Yacovlev E, Gelfand Y, et al. Pretransplant treatment of donor with immunomodulators to control graft-versus-host disease (GVHD) in transplant recipients. Exp Hematol. 2007;35:748–756
  25. Morecki S, Panigrahi S, Pizov G, et al. Effect of KRN7000 on induced graft-vs-host disease. Exp Hematol. 2004;32:630–637
  26. Kaplan E, Meier P. Non-parametric estimation from incomplete observation. J Am Stat Assoc. 1958;53:457–482
  27. Mantel E. Evaluation of survival data and two new rank orders statistics arising in its consideration. Cancer Chemother. 1966;50:163–170
  28. Sparwasser T, Hultner L, Koch ES, et al. Immunostimulatory CpG-oligodeoxynucleotides cause extramedullary murine hemopoiesis. J Immunol. 1999;162:2368–2384
  29. Melani C, Chiodoni C, Forni G, et al. Myeloid cell expansion elicited by the progression of spontaneous mammary carcinomas in c-erbB-2 transgenic BALB/c mice suppresses immune reactivity. Blood. 2003;102:2138–2145
  30. Young MR, Wright MA, Matthews JP, et al. Suppression of T cell proliferation by tumor-induced granulocyte-macrophage progenitor cells producing transforming growth factor-beta and nitric oxide. J Immunol. 1996;156:1916–1922
  31. Almand B, Clark JI, Nikitina E, et al. Incerased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol. 2001;166:678–689
  32. Delano MJ, Scumpia PO, Weinstein JS, et al. MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T cell suppression and Th2 polarization in sepsis. J Exp Med. 2007;204:1463–1474
  33. Ezernitchi AV, Vaknin I, Cohen-Daniel L, et al. TCR ζ down-regulation under chronic inflammation is mediated by myeloid suppressor cells differentially distributed between various lymphatic organs. J Immunol. 2006;177:4763–4772
  34. Pelaez B, Campillo JA, Lopez-Asenjo JA, et al. Cyclophosphamide induces the development of early myeloid cells suppressing tumor cell growth by a nitric oxide-dependent mechanism. J Immunol. 2001;166:6608–6615
  35. Billiau AD, Fevery S, Rutgeerts O, et al. Transient expansion of Mac1+Ly6-G+Ly6-C+ early myeloid cells with suppressor activity in spleens of murine radiation marrow chimeras: possible implication for the graft-versus-host and graft-versus-leukemia reactivity of donor lymphocyte infusions. Blood. 2003;102:740–748
  36. Robner S, Voigtlander C, Wiethe C, et al. Myeloid dendritic cell precursors generated from bone marrow suppress T cell responses via cell contact and nitric oxide production in vitro. Eur J Immunol. 2005;35:3533–3544
  37. Serafini P, De Santo C, Marigo I, et al. Derangement of immune responses by myeloid suppressor cells. Cancer Immunol Immunother. 2004;53:64–72
  38. Kesherwani V, Sodhi A. Differential activation of macrophages in vitro by lectin Concanavalin A, phytohemagglutinin, and wheat germ agglutinin: production and regulation of nitric oxide. Nitric Oxide. 2007;16:294–305
  39. Hibbs JB, Taintor RR, Vavrin Z, et al. Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun. 1988;157:87–94
  40. Kuvibidila SR, Velez M, Yu L, et al. Differences in iron requirements by concanvalin A–treated and anti-CD3–treated murine splenic lymphocytes. Br J Nutr. 2002;88:67–72
  41. Abel K, Wang Y, Fritts L, et al. Deoxycytidyl-deoxyguanosine oligonucleotide class A, B, and C induce distinct cytokine gene expression patterns in rhesus monkey peripheral blood mononuclear cells and distinct alpha interferon responses in TLR9-expressing rhesus monkey plasmacytoid dendritic cells. Clin Diagn Lab Immunol. 2005;12:606–621
  42. Lucey DR, Clerici M, Shearer GM. Type 1 and type 2 cytokine dysregulation in human infectious neoplastic and inflammatory diseases. Clin Microbiol Rev. 1996;9:532–562
  43. Anitescu M, Chace JH, Tuetken R, et al. Interleukin-10 functions in vitro and in vivo to inhibit bacterial DNA-induced secretion of interleukin-12. J Interferon Cytokine Res. 1997;17:781–788
  44. Blazar BR, Kried AM, Taylor PA. Synthetic unmethylated cytosine-phosphate-guanosine oligodeoxynucleotide are potent stimulators of antileukemia responses in naïve and bone marrow transplant recipients. Blood. 2001;98:1217–1225
  45. Senuma A, Hagiwara E, Nagahama K, et al. Therapeutic effect of CpG motifs on the development of chronic graft-versus-host disease in mice. Cytokine. 2002;20:23–29
  46. Lamb RJ, Capocasale RJ, Duffy KE, et al. Identification and characterization of novel bone marrow myeloid DEC205+Gr-1+ cell subsets that differentially express chemokine and TLRs. J Immunol. 2007;178:7833–7839
  47. Kuwatani M, Ikarashi Y, Mineishi S, et al. An irradiation-free nonmyeloablative bone marrow transplantation model: importance of the balance between donor T-cell number and the intensity of conditioning. Transplantation. 2005;80:1145–1152
  48. Mellor AL, Baban B, Chandler PR, et al. Cutting edge: CpG oligonucleotides induce splenic CD19+ dendritic cells to acquire potent indoleamine 2,3-dioxygenase–dependent T cell regulatory functions via IFN type 1 signaling. J Immunol. 2005;175:5601–5605
  49. Wu HJ, Sawaya H, Binstadt B, et al. Inflammatory arthritis can be reined in by CpG- induced DC-NK cell cross-talk. J Exp Med. 2007;204:1911–1922
  50. Schultz KR, Su WN, Hsiao CC, et al. Chloroquine prevention of murine MHC- disparate acute graft-versus-host disease correlates with inhibition of splenic response to CpG oligodeoxynucleotide and alteration in T cell cytokine production. Biol Blood Marrow Transplant. 2002;8:648–655
  51. Li JM, Waller EK. Donor antigen-presenting cells regulate T cell expansion and antitumor activity after allogeneic bone marrow transplantation. Biol Blood Marrow Transplant. 2004;10:540–551
  52. Li JM, Gorechlad J, Larsen CP, et al. Apoptotic donor leukocyte limit mixed-chimerism induced by CD40-CD154 blockade in allogeneic bone marrow transplantation. Biol Blood Marrow Transplant. 2006;12:1239–1249
  53. Cohen JL, Salomon BL. Therapeutic potential of CD4+CD25+ regulatory T cells in allogeneic transplantation. Cytotherapy. 2005;7:166–170
  54. Sprangers B, Fevery S, Van Wijmeersch B, et al. Can graft-versus-leukemia reactivity be dissociated from graft-versus-host disease?. Front Biosci. 2007;12:4568–4594

PII: S1083-8791(08)00278-4

doi: 10.1016/j.bbmt.2008.06.018

Biology of Blood and Marrow Transplantation
Volume 14, Issue 9 , Pages 973-984 , September 2008

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