scholarly journals Recovery of contact hypersensitivity responses following murine bone marrow transplantation: comparison of gamma-irradiation and busulfan as preparative marrow-ablative agents

Blood ◽  
1987 ◽  
Vol 70 (6) ◽  
pp. 1910-1920
Author(s):  
WE Samlowski ◽  
CL Crump
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Gamma Irradiation ◽  
Immune Function ◽  
Marrow Transplantation ◽  
Contact Hypersensitivity ◽  
Whole Body ◽  
Tissue Specific ◽  
Murine Bone Marrow ◽  
Specific Localization

Bone marrow transplantation (BMT) is often followed by significant morbidity and mortality due to protracted immunodeficiency. We have hypothesized that the bone marrow-ablative regimen may delay the recovery of normal immune function following transplantation by impairing the interaction of host endothelial cells with circulating graft-derived lymphocytes. This report compares the relative effects of busulfan (an alkylating drug) and gamma-irradiation on the tissue- specific localization potential of lymphocytes and the eventual recovery of immune function within syngeneic murine transplant recipients. Localization of normal lymphocytes into peripheral lymph nodes of irradiated BMT recipients was markedly less (less than 50%) than in busulfan-treated or normal mice over the first 2 months post- BMT. This finding correlated with irradiation-induced endothelial cell edema and microvascular occlusions within lymphocyte-receptive areas of the nodal microvasculature. The effect of both preparative regimens on the recovery of contact hypersensitivity (CHS) was also analyzed. This response recovered more quickly (between 1 and 2 months) in busulfan- pretreated animals. Further experiments demonstrated that the decrease in CHS responsiveness appeared, in part, related to a depression in the capacity of lymphocytes to localize into skin sites of antigen deposition within irradiated mice. The impairment of tissue-specific lymphocyte localization may represent a novel mechanism by which whole body irradiation can contribute to delayed immunologic reconstitution following bone marrow transplantation.

scholarly journals Recovery of contact hypersensitivity responses following murine bone marrow transplantation: comparison of gamma-irradiation and busulfan as preparative marrow-ablative agents

Blood ◽  
1987 ◽  
Vol 70 (6) ◽  
pp. 1910-1920 ◽  
Author(s):  
WE Samlowski ◽  
CL Crump
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Gamma Irradiation ◽  
Immune Function ◽  
Marrow Transplantation ◽  
Contact Hypersensitivity ◽  
Whole Body ◽  
Tissue Specific ◽  
Murine Bone Marrow ◽  
Specific Localization

Abstract Bone marrow transplantation (BMT) is often followed by significant morbidity and mortality due to protracted immunodeficiency. We have hypothesized that the bone marrow-ablative regimen may delay the recovery of normal immune function following transplantation by impairing the interaction of host endothelial cells with circulating graft-derived lymphocytes. This report compares the relative effects of busulfan (an alkylating drug) and gamma-irradiation on the tissue- specific localization potential of lymphocytes and the eventual recovery of immune function within syngeneic murine transplant recipients. Localization of normal lymphocytes into peripheral lymph nodes of irradiated BMT recipients was markedly less (less than 50%) than in busulfan-treated or normal mice over the first 2 months post- BMT. This finding correlated with irradiation-induced endothelial cell edema and microvascular occlusions within lymphocyte-receptive areas of the nodal microvasculature. The effect of both preparative regimens on the recovery of contact hypersensitivity (CHS) was also analyzed. This response recovered more quickly (between 1 and 2 months) in busulfan- pretreated animals. Further experiments demonstrated that the decrease in CHS responsiveness appeared, in part, related to a depression in the capacity of lymphocytes to localize into skin sites of antigen deposition within irradiated mice. The impairment of tissue-specific lymphocyte localization may represent a novel mechanism by which whole body irradiation can contribute to delayed immunologic reconstitution following bone marrow transplantation.

scholarly journals Therapy of Acute Leukemia by Whole-Body Irradiation and Bone Marrow Transplantation from an Identical Normal Twin

Blood ◽  
1959 ◽  
Vol 14 (3) ◽  
pp. 228-234 ◽  
Author(s):  
JOHN B. ATKINSON ◽  
FRANCIS J. MAHONEY ◽  
IRVING R. SCHWARTZ ◽  
JOSEPH A. HESCH
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Acute Leukemia ◽  
Marrow Transplantation ◽  
Whole Body ◽  
Normal Twin

Specific Non-Responsiveness to Pig in Baboons Receiving BMT from GalT-KO Pigs.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5265-5265 ◽  
Author(s):  
Ahmed Ghazi ◽  
Adam Griesemer ◽  
Masayoshi Okumi ◽  
Erica Hirsh ◽  
Diana Lo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Bone Marrow Transplantation ◽  
Nonhuman Primate ◽  
Marrow Transplantation ◽  
Progenitor Cell ◽  
Cytotoxicity Assay ◽  
Whole Body ◽  
Serum Antibodies ◽  
Cell Engraftment

Abstract Background: The induction of stable hematopoietic cell chimerism through bone marrow transplantation (BMT) has been demonstrated to induce donor-specific tolerance in rodent, porcine, nonhuman primate, and human clinical allogenic models, and has also been successful in concordant rodent and nonhuman primate xenogeneic models, as well as in the pig-to-NOD/SCID humanized mouse xenogenic model. However, stable chimerism and tolerance has been difficult to achieve in the discordant pig-to-baboon xenotransplantation model, possibly due in part to the presence in baboons of pre-formed natural xeno-reactive antibodies to a1,3-galactose (Gal) determinants expressed in pigs, but not in Old World primates and humans. The recent availability of miniature swine homozygous for a disruption in the gene encoding a1,3-galactosyltransferase (GalT-KO pigs) has now made it possible to study pig-to-baboon xenografts in the absence of effects of anti-Gal antibodies. We have investigated the GalT-KO pig-to-baboon model further by modifying the conditioning and immunosuppression regimen to facilitate engraftment and tolerance through bone marrow transplantation. Methods: BM was harvested from GalT-KO swine (n=3). Baboons (n=3) were pre-treated with whole body (3 Gy) and thymic (7 Gy) irradiation, Sangstat rabbit anti-thymocyte globulin (ATG), LoCD2b (rat IgG2b anti-primate CD2) and splenectomy, and received FK506 immunosuppressive and supportive therapy for 28 days. The baboons were monitored for the presence of pig cells by flow cytometry, for porcine progenitor cells in the bone marrow by porcine cytochrome b specific PCR of colony-forming units (CFUs), and for cellular reactivity to pig cells by MLR and CML. Antibody formation to LoCD2b and ATG was tested by enzyme-linked immunosorbent assay (ELISA), and antibody reactivity to GalT-KO pig cells was tested by flow cytometry and antibody mediated cytotoxicity assay. Results: A mean of 1.4 × 109 BM cells/kg was infused into each baboon. Although pig cells were undetectable in the peripheral blood of the baboons by flow cytometry, porcine progenitor cell engraftment as well as chimerism in the bone marrow and thymus was detected by PCR in the first baboon on day 28. ELISA results indicated the presence of antibodies to rat (LoCD2b) and rabbit (ATG) immunoglobulin within two weeks; however, no antibodies to pig cells could be detected by flow cytometry or cytotoxicity assay. The second baboon had undetectable serum antibodies to pig cells for 60 days despite the presence of induced antibodies to rat LoCD2b and rabbit ATG. Porcine progenitor cell engraftment was confirmed by PCR of CFUs on day 60 and MLR showed no response to pig although the animal regained alloresponses by this time. The third baboon, in contrast, had detectable induced serum antibodies to pig cells as well as rat and rabbit immunoglobulin by day 14 following BMT. Conclusions: Engraftment has been achieved following GalT-KO pig-to-baboon BMT with evidence of specific humoral and cellular non-responsiveness to pig cells (2/3 baboons), suggesting the possibility that this protocol may facilitate xenograft tolerance.

Timing of neutrophil tissue repopulation predicts restoration of innate immune protection in a murine bone marrow transplantation model

Blood ◽  
2006 ◽  
Vol 108 (8) ◽  
pp. 2821-2826 ◽  
Author(s):  
Chrisovalantou Cheretakis ◽  
Roland Leung ◽  
Chun Xiang Sun ◽  
Yigal Dror ◽  
Michael Glogauer
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Fluorescent Protein ◽  
Innate Immune ◽  
Bacterial Killing ◽  
Murine Bone Marrow ◽  
Susceptibility To Infection ◽  
Oral Rinse

Abstract It has been suggested that neutrophil tissue repopulation following bone marrow transplantation (BMT) serves as an earlier and more relevant marker of susceptibility to infection than circulating neutrophil counts. In a previous study using an oral rinse protocol, we found that oral neutrophil recovery always preceded blood neutrophil engraftment and that the day of oral neutrophil detection served as a predictor of patient susceptibility to infection after BMT. Consequently, we have developed and validated a mouse BMT model which uses bone marrow transplants containing enhanced green fluorescent protein-expressing neutrophils to follow neutrophil tissue repopulation after BMT. Using this in vivo cell migration model, we assessed the significance of neutrophil tissue recruitment kinetics with neutrophil functionality and in vivo bacterial killing after BMT. Using the animal model, we have demonstrated that protection against bacterial infection is conferred at the time of neutrophil tissue delivery, which always occurs before neutrophils are detected in the blood. We therefore conclude that neutrophil tissue recovery is an early measure of the restoration of cellular innate immune function after BMT. This model will help us better understand the factors regulating neutrophil recruitment to the tissues.

scholarly journals 52Fe for additional marrow ablation before bone marrow transplantation

Blood ◽  
1993 ◽  
Vol 81 (12) ◽  
pp. 3435-3439 ◽  
Author(s):  
A Ferrant ◽  
M Cogneau ◽  
N Leners ◽  
F Jamar ◽  
P Martiat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Conditioning Regimen ◽  
Absorbed Dose ◽  
Hematologic Malignancies ◽  
Whole Body ◽  
Median Percentage ◽  
Preparative Regimen

Abstract The effectiveness of bone marrow transplantation (BMT) for malignant blood diseases remains limited by the inability of the preparative regimen to eliminate the disease without causing toxicity to normal organs. We have used 52Fe to deliver radiotherapy selectively to the BM. Fourteen patients with hematologic malignancies received 52Fe before a conventional BMT conditioning regimen. The median 52Fe dose was 58 mCi (range, 32 to 85 mCi). As evaluated by quantitative scanning, the median percentage of 52Fe taken up by the BM was 82% (range, 36% to 90%). This resulted in a median radiation-absorbed dose to the BM of 632 rad (range, 151 to 1,144 rad). The median uptake of 52Fe by the liver was 18% (range, 10% to 64%) and the median radiation-absorbed dose to the liver was 239 rad (range, 82 to 526 rad). The median whole body radiation-absorbed dose was 46 rad (range, 22 to 68 rad). No untoward effects were noted after the injections of 52Fe. The patients recovered hematopoiesis without toxicity in excess of that expected with conventional conditioning alone. The median follow-up was 8 months and three patients have relapsed. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before marrow transplantation without increasing toxicity.

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