Experimental Hematology
Volume 37, Issue 6 , Pages 744-754 , June 2009

Factor VIII−pulsed dendritic cells reduce anti−factor VIII antibody formation in the hemophilia A mouse model

  • Margaret V. Ragni

      Affiliations

    • Medicine/Hematology/Oncology, University of Pittsburgh Medicine Center, Pittsburgh, Pa., USA
    • Hemophilia Center of Western Pennsylvania, Pittsburgh, Pa., USA
    • Drs. Ragni and Lu contributed equally to this work.
    • Corresponding Author InformationOffprint requests to: Margaret V. Ragni, M.D., M.P.H., Division Hematology/Oncology, University of Pittsburgh, 3636 Boulevard of the Allies, Pittsburgh, PA 15213-4306
    • ,
  • Wenhu Wu

      Affiliations

    • Starzl Transplantation Institute, Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pa., USA
    • ,
  • Xiaoyan Liang

      Affiliations

    • Starzl Transplantation Institute, Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pa., USA
    • ,
  • Ching-Chuan Hsieh

      Affiliations

    • Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
    • ,
  • Andrea Cortese-Hassett

      Affiliations

    • The Institute for Transfusion Medicine, Pittsburgh, Pa., USA
    • ,
  • Lina Lu

      Affiliations

    • Starzl Transplantation Institute, Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pa., USA
    • Drs. Ragni and Lu contributed equally to this work.
    • Current address: Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, NE40, Cleveland, OH 44195.

Received 14 December 2008 ,Revised 21 February 2009 ,Accepted 23 February 2009.

References 

  1. Astermark J. Basic aspects of inhibitors to factor VIII and IX and the influence of non-genetic risk factors. Haemophilia. 2006;12(Suppl 6):8–14
  2. Ehrenforth S, Kruetz W, Sharrer I, et al. Incidence of development of FVIII and factor IX inhibitors in hemophiliacs. Lancet. 1992;339:594–598
  3. Ragni MV, Bontempo FA, Lewis JH. Disappearance of inhibitor to factor VIII in HIV-infected hemophiliacs with progression to AIDS, severe ARC. Transfusion. 1989;29:447–449
  4. Hoyer LW, Qian J. Characterization of the immune response to factor VIII using hemophilia A mice. Haemotologica. 2000;85:100–102
  5. Qian J, Collins M, Sharpe AH, et al. Prevention and treatment of factor VIII inhibitors in murine hemophilia A. Blood. 2000;95:1324–1329
  6. Qian J, Borovok M, Bi L, Kazazian HH, Hoyer LW. Inhibitor antibody development and T cell response to human factor VIII in murine hemophilia A. Thromb Haemost. 1999;81:240–244
  7. Mukovozov I, Sablijc T, Hortelano G, Ofosu FA. Factors that contribute to the immunogenicity of therapeutic recombinant human proteins. Thromb Haemost. 2008;99:874–882
  8. Reisner JM, Clark A, Levin L. Immunogenetics of the human immune response to factor VIII. Adv Exp Biol Med. 1993;386:65–78
  9. Hu G, Guo D, Key NS, Conti-Fine BM. Cytokine production by CD4+ T cells specific for coagulation factor VIII in healthy subjects and haemophilia A patients. Thromb Haemost. 2007;97:788–794
  10. Powrie F, Maloy KJ. Immunology: regulating the regulators. Science. 2003;299:1030–1031
  11. Jiang H, Chess L. Regulation of immune responses by T cells. N Engl J Med. 2006;354:1166–1176
  12. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299:1057–1061
  13. Lu L, Thomson AW. Manipulation of dendritic cells for tolerance induction in transplantation and autoimmune disease. Transplantation. 2002;73(Suppl 1):S19–S22
  14. Fontenot JD, Rudensky AY. A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol. 2005;6:331–337
  15. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4:330–336
  16. Macedoo C, Popescu I, Abu-Elmagd K, et al. Augmentation of type 1 polarizing ability of monocyte-derived dendritic cells from chronically immunosuppressed organ transplant recipients. Transplantation. 2005;79:451–459
  17. Ma L, Qian S, Liang X, Wang L, et al. Prevention of diabetes in NOD mice by administration of dendritic cells deficient in nuclear transcription factor-κB activity. Diabetes. 2003;52:1976–1985
  18. Bi L, Lawler AM, Antonarakis SE, et al. Targeted disruption of the mouse factor VIII gene produces a model of hemophilia A. Nat Genet. 1995;10:119–121
  19. Bi L, Sarkar R, Haas T, et al. Further characterization of factor VIII-deficient mice created by gene targeting: RNA and protein studies. Blood. 1996;88:3446–3450
  20. Bonham CA, Peng L, Liang X, et al. Marked prolongation of cardiac allograft survival by dendritic cells genetically engineered with NF-κB oligodeoxyribonucleotide decoys and adenoviral vectors encoding CTLA4-Ig. J Immunol. 2002;169:3382–3391
  21. Lu L, McCaslin D, Starzl TE, et al. Bone marrow-derived dendritic cell progenitors (NLDC 145+, MHC class II+, B7-1dim, B7-2−) induce alloantigen-specific hyporesponsiveness in murine T lymphocytes. Transplantation. 1995;60:1539–1545
  22. Lu L, Qian S, Hershberger PA, et al. Fas ligand (CD95L) and B7 expression on dendritic cells provide counter-regulatory signals for T-cell survival and proliferation. J Immunol. 1997;158:5676–5684
  23. Ling M, Duncan EM, Rodgers SE, et al. Low detection rate of antibodies to non-functional epitopes on factor VIII in patients with hemophilia A and negative for inhibitors by Bethesda assay. J Thromb Haemost. 2003;1:2548–2553
  24. Sun CM, Hall JA, Blank RB, et al. Small intestine lamina propria dendritici cells promote de novo generation of FoxP3 T reg cells via retinoic acid. J Exp Med. 2007;204:1775–1785
  25. Kasper CK, Aledort LM, Counts RB, et al. A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh. 1975;34:869–872
  26. Llorente L, Zou W, Levy Y, et al. Role of interleukin-10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med. 1995;181:839–844
  27. Lozier JN, Tayebi N, Zhang P. Mapping of genes that control the antibody response to human factor IX in mice. Blood. 2005;105:1029–1035
  28. Astermark J, Oldenburg J, Parlova A, Berntorp E, Lefvert AK. Polymorphisms in the IL-10 but not in the IL1β and IL4 genes are associated with inhibitor development in patients with hemophilia A. Blood. 2006;107:3167–3172
  29. Mingozzi F, Maus MV, Hui DJ, et al. CD8+ T-cell responses to adeno-associated virus capsid in humans. Nat Med. 2007;13:419–422
  30. Morelli AE, Coates PTH, Shufesky WJ, et al. Growth factor-induced mobilization of dendritic cells in kidney and liver of rhesus macaques: implications for transplantation. Transplantation. 2007;83:656–662
  31. Trucco M, Giannoukakis N. Immunoregulatory dendritic cells to prevent and reverse new-onset type 1 diabetes mellitus. Expert Opin Biol Ther. 2007;7:951–963

PII: S0301-472X(09)00059-9

doi: 10.1016/j.exphem.2009.02.011

Experimental Hematology
Volume 37, Issue 6 , Pages 744-754 , June 2009

Article Tools

* Image Usage & Resolution