|
|
 Previous Article | Table of Contents | Next Article 
Impact of pretransplant conditioning and donor T cells on chimerism,
graft-versus-host disease, graft-versus-leukemia reactivity, and tolerance
after bone marrow transplantation
RL Truitt and AA Atasoylu
Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226.
Graft rejection, mixed chimerism, graft-versus-host disease (GVHD),
leukemia relapse, and tolerance are interrelated manifestations of
immunologic reactivity between donor and host cells that significantly
affect survival after allogeneic bone marrow transplantation (BMT). In this
report, a mouse model of BMT, in which the donor and host were compatible
at the major histocompatibility complex (MHC), was used (1) to examine the
interrelationship of pretransplant conditioning and T- cell content of
donor BM with regard to lymphoid chimerism and GVHD and (2) to determine
how these factors affected graft-versus-leukemia (GVL) reactivity and
donor-host-tolerance. AKR (H-2k) host mice were administered optimal or
suboptimal total body irradiation (TBI) as pretransplant conditioning
followed by administration of BM cells from B10.BR (H-2k) donor mice with
or without added spleen cells as a source of T lymphocytes. Transplanted
mice were injected with a supralethal dose of AKR leukemia cells 20 and 45
days post-BMT to assess GVL reactivity in vivo. The pretransplant
conditioning of the host and T- cell content of the donor marrow affected
the extent of donor T-cell chimerism and the severity of GVH disease. GVL
reactivity was dependent on transplantation of mature donor T cells and
occurred only in complete chimeras. Transplantation of T-cell-deficient BM
resulted in the persistence of host T cells, ie, incomplete donor T-cell
chimerism, even when lethal TBI was used. Mixed chimerism was associated
with a lack of GVL reactivity, despite the fact that similar numbers of
donor T cells were present in the spleens of mixed and complete chimeras.
In this model, moderate numbers of donor T cells facilitated complete donor
T-cell engraftment, caused only mild GVHD, and provided a significant GVL
effect without preventing the subsequent development of tolerance after
conditioning with suboptimal TBI. In contrast, severe, often lethal, GVHD
developed when the dose of TBI was increased, whereas tolerance and no
GVH/GVL reactivity developed when the T-cell content of the marrow was
decreased.
Volume 77,
Issue 11,
pp. 2515-2523,
06/01/1991
Copyright © 1991 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Eto, Y. Kamiryo, A. Takeuchi, M. Harano, K. Tatsugami, M. Harada, K. Kiyoshima, M. Hamaguchi, T. Teshima, M. Tsuneyoshi, et al.
Posttransplant Administration of Cyclophosphamide and Donor Lymphocyte Infusion Induces Potent Antitumor Immunity to Solid Tumor
Clin. Cancer Res.,
May 1, 2008;
14(9):
2833 - 2840.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Eto, M. Harano, K. Tatsugami, M. Harada, Y. Kamiryo, K. Kiyoshima, M. Hamaguchi, M. Tsuneyoshi, Y. Yoshikai, and S. Naito
Cyclophosphamide-Using Nonmyeloablative Allogeneic Cell Therapy against Renal Cancer with a Reduced Risk of Graft-versus-Host Disease
Clin. Cancer Res.,
February 1, 2007;
13(3):
1029 - 1035.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Harano, M. Eto, T. Iwai, K. Tatsugami, K. Kiyoshima, Y. Kamiryo, M. Tsuneyoshi, Y. Yoshikai, and S. Naito
Renal Cancer Treatment with Low Levels of Mixed Chimerism Induced by Nonmyeloablative Regimen Using Cyclophosphamide in Mice
Cancer Res.,
November 1, 2005;
65(21):
10032 - 10040.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Nakamura, M. Inaba, K. Sugiura, T. Yoshimura, A-H. Kwon, Y. Kamiyama, and S. Ikehara
Enhancement of Allogeneic Hematopoietic Stem Cell Engraftment and Prevention of GvHD by Intra-Bone Marrow Bone Marrow Transplantation Plus Donor Lymphocyte Infusion
Stem Cells,
March 1, 2004;
22(2):
125 - 134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Luznik, J. E. Slansky, S. Jalla, I. Borrello, H. I. Levitsky, D. M. Pardoll, and E. J. Fuchs
Successful therapy of metastatic cancer using tumor vaccines in mixed allogeneic bone marrow chimeras
Blood,
February 15, 2003;
101(4):
1645 - 1652.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. D. Billiau, S. Fevery, O. Rutgeerts, W. Landuyt, and M. Waer
Crucial role of timing of donor lymphocyte infusion in generating dissociated graft-versus-host and graft-versus-leukemia responses in mice receiving allogeneic bone marrow transplants
Blood,
August 13, 2002;
100(5):
1894 - 1902.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Luznik, S. Jalla, L. W. Engstrom, R. Iannone, and E. J. Fuchs
Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide
Blood,
December 1, 2001;
98(12):
3456 - 3464.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Matsue, K. Matsue, M. Kusuhara, T. Kumamoto, K. Okumura, H. Yagita, and A. Takashima
Immunosuppressive properties of CD95L-transduced "killer" hybrids created by fusing donor- and recipient-derived dendritic cells
Blood,
December 1, 2001;
98(12):
3465 - 3472.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. d. C. Bittencourt, S. Perruche, E. Contassot, S. Fresnay, M.-H. Baron, R. Angonin, F. Aubin, P. Herve, P. Tiberghien, and P. Saas
Intravenous injection of apoptotic leukocytes enhances bone marrow engraftment across major histocompatibility barriers
Blood,
July 1, 2001;
98(1):
224 - 230.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. R. Hill and J. L. M. Ferrara
The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation
Blood,
May 1, 2000;
95(9):
2754 - 2759.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. D. Shlomchik, M. S. Couzens, C. B. Tang, J. McNiff, M. E. Robert, J. Liu, M. J. Shlomchik, and S. G. Emerson
Prevention of Graft Versus Host Disease by Inactivation of Host Antigen-Presenting Cells
Science,
July 16, 1999;
285(5426):
412 - 415.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
G. Shankar, J. Scott Bryson, C. Darrell Jennings, A. M. Kaplan, and D. A. Cohen
Idiopathic Pneumonia Syndrome after Allogeneic Bone Marrow Transplantation in Mice . Role of Pretransplant Radiation Conditioning
Am. J. Respir. Cell Mol. Biol.,
June 1, 1999;
20(6):
1116 - 1124.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
H. Baurmann, S. Nagel, T. Binder, A. Neubauer, W. Siegert, and D. Huhn
Kinetics of the Graft-Versus-Leukemia Response After Donor Leukocyte Infusions for Relapsed Chronic Myeloid Leukemia After Allogeneic Bone Marrow Transplantation
Blood,
November 15, 1998;
92(10):
3582 - 3590.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. R. Hill, J. M. Crawford, K. R. Cooke, Y. S. Brinson, L. Pan, and J. L.M. Ferrara
Total Body Irradiation and Acute Graft-Versus-Host Disease: The Role of Gastrointestinal Damage and Inflammatory Cytokines
Blood,
October 15, 1997;
90(8):
3204 - 3213.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Or, L. Weiss, and S. Teiman
Fludarabine Monophosphate Reduces the Incidence and Severity of Graft-Versus-Host Disease in a Murine Model of Bone Marrow Transplantation
Blood,
July 1, 1997;
90(1):
471 - 471.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. R. Drobyski and D. Majewski
Donor gamma delta T Lymphocytes Promote Allogeneic Engraftment Across the Major Histocompatibility Barrier in Mice
Blood,
February 1, 1997;
89(3):
1100 - 1109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
