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.
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References
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
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
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
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
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
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
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
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
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
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
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
Smith LH, Vos O . Radiation sensitivity of mouse lymph node cells relative to their proliferative capacity in vivo Radiat Res 1963 19: 485–491
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
Miyakoshi J, Tatsumi K, Takebe H . Radiation sensitivity of T-lymphocytes grown with recombinant human IL-2 Mutat Res 1987 192: 163–167
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
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
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
Vriesendorp HM, Chu H, Ochran TG et al. Radiobiology of total body radiation Bone Marrow Transplant 1994 14: (Suppl. 4) S4–8
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
Pestronk A, Drachman DB, Teoh R, Adams RN . Combined short-term immunotherapy for experimental autoimmune myasthenia gravis Ann Neurol 1983 14: 235–241
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
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
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
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
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
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.
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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
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DOI: https://doi.org/10.1038/sj.bmt.1702153
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