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:

Conditioning Regimens

Conditioning regimens for the treatment of experimental arthritis with autologous bone marrow transplantation

Abstract

Adjuvant induced arthritis (AA) in Buffalo rats is a chronic progressive disease that responds very well to treatment with myeloablation and rescue with autologous BM. These previous results were obtained by conditioning with a lethal single dose of TBI. In the present study various other conditioning regimens were compared with single dose TBI. Fractionated TBI using adjusted total dose was equally effective. CY and BU when used as single agents at the highest tolerated dose were less effective. Combinations of CY (2 × 60 mg/kg) with lower dose (4 Gy) TBI and of BU with CY were as beneficial as high-dose TBI. These results indicate that a very intense reduction of T lymphocytes, in the order of 3–4 log, is required for obtaining the highest rate of long-lasting complete remissions. A similar conclusion was reached from our studies of various conditioning regimens in rats suffering from experimental allergic encephalitis (EAE). If extrapolated to the clinic, such a degree of T lymphocyte eradication poses upper limits to the number of T lymphocytes that can be safely reintroduced with the autograft. The exact limits cannot be derived from these experiments because the addition of autologous T lymphocytes to the graft yielded different results in the two models of autoimmune disease (AID). Bone Marrow Transplantation (2000) 25, 357–364.

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

Access options

Buy this article

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. Van Bekkum DW, Bohre EPM, Houben PFJ, Knaan-Shanzer S . Regression of adjuvant-induced arthritis in rats following bone marrow transplantation Proc Natl Acad Sci USA 1989 86: 10090–10094

    Article  CAS  Google Scholar 

  2. Van Gelder M, Van Bekkum DW . Treatment of relapsing experimental autoimmune encephalomyelitis in rats with allogeneic bone marrow transplantation from a resistant strain Bone Marrow Transplant 1995 16: 343–351

    CAS  PubMed  Google Scholar 

  3. Van Gelder M, Mulder AH, van Bekkum DW . Treatment of relapsing experimental autoimmune encephalomyelitis with largely MHC-matched allogeneic bone marrow transplantation Transplantation 1996 62: 810–818

    Article  CAS  Google Scholar 

  4. Ikehara S, Yasumizu R, Inaba M et al. Long-term observations of autoimmune-prone mice treated for autoimmune disease by allogeneic bone marrow tranplantation Immunology 1989 86: 3306–3310

    CAS  Google Scholar 

  5. Marmont AM . Immune ablation followed by allogeneic or autologous bone marrow transplantation: a new treatment for severe autoimmune diseases? Stem Cells 1994 12: 125–135

    Article  CAS  Google Scholar 

  6. Nelson JL, Torrez R, Louie FM et al. Pre-existing autoimmune disease in patients with long-term survival after allogeneic bone marrow transplantation J Rheumatol Suppl 1997 48: 23–29

    CAS  PubMed  Google Scholar 

  7. Knaan-Shanzer S, Houben P, Kinwel-Bohre EPM, Van Bekkum DW . Remission induction of adjuvant arthritis in rats by total body irradiation and autologous bone marrow transplantation Bone Marrow Transplant 1991 8: 333–338

    CAS  PubMed  Google Scholar 

  8. Van Gelder M, Van Bekkum DW . Effective treatment of relapsing experimental autoimmune encephalomyelitis with pseudoautologous bone marrow transplantation Bone Marrow Transplant 1996 18: 1029–1034

    CAS  PubMed  Google Scholar 

  9. Pearson CM, Wood FD . Studies of arthritis and other lesions induced in rats by the injection of mycobacterial adjuvant Am J Pathol 1963 42: 73–95

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Van Bekkum DW . Foreign bone marrow transplantation following fractionated whole-body irradiation in mice. In: Ebert M, Howard A (eds) Radiation Effects in Physics, Chemistry and Biology North Holland Press: Amsterdam 1963 p 362

    Google Scholar 

  11. Vriesendorp HM . Engraftment of hemopoietic cells. In: Bekkum DW, LoÐwenberg B (eds) Bone Marrow Transplantation Biological Mechanisms and Clinical Practice Marcel Dekker: New York 1985 p 86

    Google Scholar 

  12. Smith LH, Vos O . Radiation sensitivity of mouse lymph node cells relative to their proliferative capacity in vivo Radiat Res 1963 19: 485–491

    Article  Google Scholar 

  13. James SE, Arlett CF, Green MH, Bridges BA . Radiosensitivity of human T-lymphocytes proliferating in long term culture Int J Radiat Biol 1983 44: 417–422

    CAS  Google Scholar 

  14. Miyakoshi J, Tatsumi K, Takebe H . Radiation sensitivity of T-lymphocytes grown with recombinant human IL-2 Mutat Res 1987 192: 163–167

    Article  CAS  Google Scholar 

  15. Stewart CC, Stevenson AP, Habbersett RC . The effect of low dose irradiation on unstimulated and PHA-stimulated human lymphocyte subsets Int J Radiat Biol 1988 53: 77–87

    Article  CAS  Google Scholar 

  16. Dohi S, Norimura T, Kunugita N, Tsuchiya T . Determination of in vivo and in vitro radiosensitivity of mouse splenic T-lymphocytes using a T-cell cloning technique Sangyo Ika Daigaku Zasshi 1989 11: 13–22

    CAS  PubMed  Google Scholar 

  17. Williams JL, Patchen ML, Darden JH, Jackson WE . Effects of radiation on survival and recovery of T lymphocyte subsets in C3H/HeN mice Exp Hematol 1994 22: 510–516

    CAS  PubMed  Google Scholar 

  18. Vriesendorp HM, Chu H, Ochran TG et al. Radiobiology of total body radiation Bone Marrow Transplant 1994 14: (Suppl. 4) S4–8

    PubMed  Google Scholar 

  19. Euler HH, Marmont AM, Bacigalupo A et al. Early recurrence or persistence of autoimmune disease after unmanipulated autologous stem cell transplantation Blood 1996 88: 3621–3625

    CAS  PubMed  Google Scholar 

  20. Pestronk A, Drachman DB, Teoh R, Adams RN . Combined short-term immunotherapy for experimental autoimmune myasthenia gravis Ann Neurol 1983 14: 235–241

    Article  CAS  Google Scholar 

  21. Orme IM . Active and memory immunity to Lysteria monocytogenes infection in mice is mediated by phenotypically distinct T cell populations Immunology 1989 68: 93–95

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Rouse BT, Hartley D, Doherty PC . Consequences of exposure to ionizing radiation for effector T cell function in vivo Viral Immunol 1989 2: 69–78

    Article  CAS  Google Scholar 

  23. Uzawa A, Suzuki G, Nakata Y et al. Radiosensitivity of CD45RO+ memory and CD45RO− naive T cells in culture Radiat Res 1994 137: 25–33

    Article  CAS  Google Scholar 

  24. Hasegawa Y, Nakashima I, Ando K et al. Dynamics of cytotoxic T lymphocyte precursors in vivo assessed by change in the radiation sensitivity. Evidence for development of radiation-sensitive memory cells without clonal expansion Scand J Immunol 1988 28: 43–53

    Article  CAS  Google Scholar 

  25. Wulffraat N, van Royen A, Bierings M et al. Autologous haemopoietic stem-cell transplantation in four patients with refractory juvenile chronic arthritis Lancet 1999 353: 550–553

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The author gratefully acknowledges the skilled technical assistance of Els Kinwel-Bohré. The rats used in this study were paid for by the Dutch Rheuma Fund.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

van Bekkum, D. Conditioning regimens for the treatment of experimental arthritis with autologous bone marrow transplantation. Bone Marrow Transplant 25, 357–364 (2000). https://doi.org/10.1038/sj.bmt.1702153

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1702153

Keywords

This article is cited by

Search

Quick links