Biology of Blood and Marrow Transplantation
Volume 13, Issue 6 , Pages 644-654 , June 2007

In Vitro Methotrexate as a Practical Approach to Selective Allodepletion

  • Atul Sathe

      Affiliations

    • Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas
    • ,
  • Sterling B. Ortega

      Affiliations

    • Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas
    • ,
  • Dorothy I. Mundy

      Affiliations

    • Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas
    • ,
  • Robert H. Collins

      Affiliations

    • Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas
    • ,
  • Nitin J. Karandikar

      Affiliations

    • Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas
    • Corresponding Author InformationCorrespondence and reprint requests: Nitin J. Karandikar, MD, PhD, Department of Pathology, The University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9072.

Received 3 January 2007 ,Accepted 21 January 2007.

References 

  1. Appelbaum FR. The current status of hematopoietic cell transplantation. Annu Rev Med. 2003;54:491–512
  2. Ferrara JLM, Deeg HJ. Graft-versus-host disease. N Engl J Med. 1991;324:667–674
  3. Weisdorf D, Haake R, Blazar B, et al. Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome. Blood. 1990;75:1024–1030
  4. Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006;354:1813–1826
  5. Couriel D, Caldera H, Champlin R, Komanduri K. Acute graft-versus-host disease: pathophysiology, clinical manifestations, and management. Cancer. 2004;101:1936–1946
  6. Rieger K, Loddenkemper C, Maul J, et al. Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GVHD. Blood. 2006;107:1717–1723
  7. Miura Y, Thoburn CJ, Bright EC, et al. Association of Foxp3 regulatory gene expression with graft-versus-host disease. Blood. 2004;104:2187–2193
  8. Jones SC, Murphy GF, Korngold R. Post-hematopoietic cell transplantation control of graft-versus-host disease by donor CD425 T cells to allow an effective graft-versus-leukemia response. Biol Blood Marrow Transplant. 2003;9:243–256
  9. Ferrara JL, Cooke KR, Teshima T. The pathophysiology of acute graft-versus-host disease. Int J Hematol. 2003;78:181–187
  10. Ferrara JLM, Levy R, Chao NJ. Pathophysiologic mechanisms of acute graft-vs.-host disease. Biol Blood Marrow Transplant. 1999;5:347–356
  11. Kernan NA, Bordignon C, Heller G, et al. Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: I (Analysis of risk factors and results of secondary transplants). Blood. 1989;74:2227–2236
  12. Delain M, Cahn JY, Racadot E, et al. Graft failure after T cell depleted HLA identical allogeneic bone marrow transplantation: risk factors in leukemic patients. Leuk Lymphoma. 1993;11:359–368
  13. Keever CA, Small TN, Flomenberg N, et al. Immune reconstitution following bone marrow transplantation: comparison of recipients of T-cell depleted marrow with recipients of conventional marrow grafts. Blood. 1989;73:1340–1350
  14. Roux E, Helg C, Dumont-Girard F, Chapuis B, Jeannet M, Roosnek E. Analysis of T-cell repopulation after allogeneic bone marrow transplantation: significant differences between recipients of T-cell depleted and unmanipulated grafts. Blood. 1996;87:3984–3992
  15. Horowitz MM, Gale RP, Sondel PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990;75:555–562
  16. Marmont AM, Horowitz MM, Gale RP, et al. T-cell depletion of HLA-identical transplants in leukemia. Blood. 1991;78:2120–2130
  17. Michalek J, Collins RH, Durrani HP, et al. Definitive separation of graft-versus-leukemia- and graft-versus-host-specific CD4+ T cells by virtue of their receptor beta loci sequences. Proc Natl Acad Sci U S A. 2003;100:1180–1184
  18. Datta AR, Barrett AJ, Jiang YZ, et al. Distinct T cell populations distinguish chronic myeloid leukaemia cells from lymphocytes in the same individual: a model for separating GVHD from GVL reactions. Bone Marrow Transplant. 1994;14:517–524
  19. Godfrey WR, Krampf MR, Taylor PA, Blazar BR. Ex vivo depletion of alloreactive cells based on CFSE dye dilution, activation antigen selection, and dendritic cell stimulation. Blood. 2004;103:1158–1165
  20. Wehler TC, Nonn M, Brandt B, et al. Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines. Blood. 2007;109:365–373
  21. Le NT, Chen BJ, Chao NJ. Selective elimination of alloreactivity from immunotherapeutic T cells by photodynamic cell purging and memory T-cell sorting. Cytotherapy. 2005;7:126–133
  22. Martins SL, St John LS, Champlin RE, et al. Functional assessment and specific depletion of alloreactive human T cells using flow cytometry. Blood. 2004;104:3429–3436
  23. Garderet L, Snell V, Przepiorka D, et al. Effective depletion of alloreactive lymphocytes from peripheral blood mononuclear cell preparations. Transplantation. 1999;67:124–130
  24. Davies JK, Koh MB, Lowdell MW. Antiviral immunity and T-regulatory cell function are retained after selective alloreactive T-cell depletion in both the HLA-identical and HLA-mismatched settings. Biol Blood Marrow Transplant. 2004;10:259–268
  25. Montagna D, Yvon E, Calcaterra V, et al. Depletion of alloreactive T cells by a specific anti-interleukin-2 receptor p55 chain immunotoxin does not impair in vitro antileukemia and antiviral activity. Blood. 1999;93:3550–3557
  26. Amrolia PJ, Muccioli-Casadei G, Yvon E, et al. Selective depletion of donor alloreactive T cells without loss of antiviral or antileukemic responses. Blood. 2003;102:2292–2299
  27. Hartwig UF, Nonn M, Khan S, Meyer RG, Huber C, Herr W. Depletion of alloreactive T cells via CD69: implications on antiviral, antileukemic and immunoregulatory T lymphocytes. Bone Marrow Transplant. 2006;37:297–305
  28. Fehse B, Goldmann M, Frerk O, Bulduk M, Zander AR. Depletion of alloreactive donor T cells using immunomagnetic cell selection. Bone Marrow Transplant. 2000;25(Suppl 2):S39–S42
  29. Fehse B, Frerk O, Goldmann M, Bulduk M, Zander AR. Efficient depletion of alloreactive donor T lymphocytes based on expression of two activation-induced antigens (CD25 and CD69). Br J Haematol. 2000;109:644–651
  30. Szabolcs P, Park KD, Marti L, et al. Superior depletion of alloreactive T cells from peripheral blood stem cell and umbilical cord blood grafts by the combined use of trimetrexate and interleukin-2 immunotoxin. Biol Blood Marrow Transplant. 2004;10:772–783
  31. Genestier L, Paillot R, Quemeneur L, Izeradjene K, Revillard J-P. Mechanisms of action of methotrexate. Immunopharmacology. 2000;47:247–257
  32. Kremer JM. Methotrexate and leflunomide: Biochemical basis for combination therapy in the treatment of rheumatoid arthritis. Semin Arthritis Rheum. 1999;29:14–26
  33. Karandikar NJ, Crawford MP, Yan X, et al. Glatiramer acetate (Copaxone) therapy induces CD8(+) T cell responses in patients with multiple sclerosis. J Clin Invest. 2002;109:641–649
  34. Crawford MP, Yan SX, Ortega SB, et al. High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay. Blood. 2004;103:4222–4231
  35. Lyons AB. Analysing cell division in vivo and in vitro using flow cytometric measurement of CFSE dye dilution. J Immunol Methods. 2000;243:147–154
  36. Genestier L, Paillot R, Fournel S, Ferraro C, Miossec P, Revillard J-P. Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. J Clin Invest. 1998;102:322–328
  37. Paillot R, Genestier L, Fournel S, Ferraro C, Miossec P, Revillard JP. Activation-dependent lymphocyte apoptosis induced by methotrexate. Transplant Proc. 1998;30:2348–2350
  38. Cronstein BN. Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis. Pharmacol Rev. 2005;57:163–172
  39. Swierkot J, Miedzybrodzki R, Szymaniec S, Szechinski J. Activation dependent apoptosis of peripheral blood mononuclear cells from patients with rheumatoid arthritis treated with methotrexate. Ann Rheum Dis. 2004;63:599–600
  40. Scheinberg P, Price DA, Ambrozak DR, Barrett AJ, Douek DC. Alloreactive T cell clonotype recruitment in a mixed lymphocyte reaction: implications for graft engineering. Exp Hematol. 2006;34:788–795
  41. Strauss G, Osen W, Debatin KM. Induction of apoptosis and modulation of activation and effector function in T cells by immunosuppressive drugs. Clin Exp Immunol. 2002;128:255–266
  42. Hoffmann P, Ermann J, Edinger M, Fathman CG, Strober S. Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med. 2002;196:389–399
  43. Taylor PA, Lees CJ, Blazar BR. The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality. Blood. 2002;99:3493–3499

PII: S1083-8791(07)00122-X

doi: 10.1016/j.bbmt.2007.01.081

Biology of Blood and Marrow Transplantation
Volume 13, Issue 6 , Pages 644-654 , June 2007

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