scholarly journals Ultraviolet irradiation of blood prevents transfusion-induced sensitization and marrow graft rejection in dogs

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 537-539 ◽  
Author(s):  
HJ Deeg ◽  
J Aprile ◽  
TC Graham ◽  
FR Appelbaum ◽  
R Storb
Keyword(s):  
Ultraviolet Irradiation ◽  
Graft Rejection ◽  
Uv Light ◽  
Canine Model ◽  
Donor Blood ◽  
Histocompatibility Antigens ◽  
Marrow Graft ◽  
Accessory Cells ◽  
In Vitro Exposure

Abstract In a canine model using DLA-identical littermate pairs, we have shown that a regimen of three transfusions of donor blood given 24, 17, and 10 days before transplant uniformly leads to marrow graft rejection, presumably due to sensitization to minor (non-DLA) histocompatibility antigens. Untransfused dogs uniformly achieve sustained engraftment. In the present study, we investigated whether the exposure of blood to ultraviolet (UV) light (220–300 nm) prior to transfusion prevented sensitization of the recipient and allowed for successful marrow engraftment. Ten dogs were each given three pretransplant transfusions from the marrow donor. Each transfusion consisted of 50 mL of whole blood exposed in vitro to UV light for a total of 1.35 J/cm2. All ten dogs achieved engraftment. In contrast, all four dogs that had received sham-exposed transfusions rejected their grafts. In vitro studies revealed that although cell viability was not affected, leukocytes contained in UV-exposed blood were unable to function as stimulator cells in mixed leukocyte cultures or as accessory cells in mitogen- stimulated cultures. These data are consistent with the hypothesis that accessory cells are involved in transfusion-induced sensitization. We conclude that in vitro exposure of blood to UV light before transfusion prevents sensitization and allows for subsequent marrow engraftment.

scholarly journals Ultraviolet irradiation of blood prevents transfusion-induced sensitization and marrow graft rejection in dogs

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 537-539 ◽  
Author(s):  
HJ Deeg ◽  
J Aprile ◽  
TC Graham ◽  
FR Appelbaum ◽  
R Storb
Keyword(s):  
Ultraviolet Irradiation ◽  
Graft Rejection ◽  
Uv Light ◽  
Canine Model ◽  
Donor Blood ◽  
Histocompatibility Antigens ◽  
Marrow Graft ◽  
Accessory Cells ◽  
In Vitro Exposure

In a canine model using DLA-identical littermate pairs, we have shown that a regimen of three transfusions of donor blood given 24, 17, and 10 days before transplant uniformly leads to marrow graft rejection, presumably due to sensitization to minor (non-DLA) histocompatibility antigens. Untransfused dogs uniformly achieve sustained engraftment. In the present study, we investigated whether the exposure of blood to ultraviolet (UV) light (220–300 nm) prior to transfusion prevented sensitization of the recipient and allowed for successful marrow engraftment. Ten dogs were each given three pretransplant transfusions from the marrow donor. Each transfusion consisted of 50 mL of whole blood exposed in vitro to UV light for a total of 1.35 J/cm2. All ten dogs achieved engraftment. In contrast, all four dogs that had received sham-exposed transfusions rejected their grafts. In vitro studies revealed that although cell viability was not affected, leukocytes contained in UV-exposed blood were unable to function as stimulator cells in mixed leukocyte cultures or as accessory cells in mitogen- stimulated cultures. These data are consistent with the hypothesis that accessory cells are involved in transfusion-induced sensitization. We conclude that in vitro exposure of blood to UV light before transfusion prevents sensitization and allows for subsequent marrow engraftment.

scholarly journals Bone marrow graft rejection as a function of antibody-directed natural killer cells.

1985 ◽  
Vol 161 (3) ◽  
pp. 563-576 ◽  
Author(s):  
J F Warner ◽  
G Dennert
Keyword(s):  
Bone Marrow ◽  
Nk Cells ◽  
Natural Killer ◽  
Graft Rejection ◽  
Transplant Rejection ◽  
Conclusive Evidence ◽  
Antigenic Determinants ◽  
Marrow Graft

There is conclusive evidence that acute bone marrow transplant rejection in lethally irradiated mice is caused by natural killer (NK) cells. The rejection of marrow allografts is exquisitely specific and is controlled by antigenic determinants encoded in or near the H-2 gene complex. The specificity of in vivo marrow graft rejection contrasts with the in vitro specificity pattern of NK cells in cytotoxicity assays. We therefore examined how NK cells cause H-2-specific marrow graft rejection in vivo. Several experimental approaches are presented that suggest that natural antibody, present in responder strains of mice, specifically directs NK cells in an antibody-dependent cytolytic and/or cytostatic reaction, resulting in marrow graft rejection. The following evidence for this mechanism is documented. The ability to reject a marrow graft can be passively transferred by serum from responder to allogeneic nonresponder mice and the specificity of rejection can be mapped within the H-2 region. Serum-induced marrow graft rejection is abrogated following depletion of immunoglobulin, and the serum of responder mice is able to induce a specific antibody-dependent cytotoxic reaction in vitro.

Non–Host-Reactive Donor CD8+ T Cells of Tc2 Phenotype Potently Inhibit Marrow Graft Rejection

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4045-4050 ◽  
Author(s):  
Daniel H. Fowler ◽  
Bernard Whitfield ◽  
Michael Livingston ◽  
Paul Chrobak ◽  
Ronald E. Gress
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Graft Rejection ◽  
Marrow Transplant ◽  
Type I ◽  
Marrow Graft ◽  
Murine Bone Marrow ◽  
Cd8 Cells ◽  
Preparative Regimen

Donor CD8+ T cells capable of host reactivity inhibit marrow graft rejection, but also generate graft-versus-host disease (GVHD). To evaluate whether the Tc1- and Tc2-type subsets of CD8 cells might inhibit rejection without host reactivity, we established an F1 into-parent murine bone marrow transplant model. Donor Tc1 and Tc2 cells were generated that preferentially secreted type I or type II cytokines; both subsets possessed potent cytolytic function, and clonally deleted host-type allospecific precursor CTL in vitro. B6 hosts receiving 950 cGy irradiation did not reject the donor marrow (F1 chimerism of 78.6%; n = 10), whereas hosts receiving 650 cGy rejected the donor marrow (3.8% chimerism; n = 8). At 650 cGy irradiation, the addition of Tc2 cells to the F1 marrow resulted in extensive F1 chimerism (70.8%) in 8 of 8 recipients; in contrast, alloengraftment was not consistently observed in mice receiving Tc1 cells or unmanipulated CD8 cells. Furthermore, when the preparative regimen was further reduced to 600 cGy, only hosts receiving the Tc2-type cells did not reject the F1 marrow. We conclude that Tc2 cells potently inhibit marrow graft rejection without inducing an alloaggressive response and that non–host-reactive Tc2 cells therefore facilitate engraftment across genetic barriers with reduced GVHD.

Non–Host-Reactive Donor CD8+ T Cells of Tc2 Phenotype Potently Inhibit Marrow Graft Rejection

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4045-4050 ◽  
Author(s):  
Daniel H. Fowler ◽  
Bernard Whitfield ◽  
Michael Livingston ◽  
Paul Chrobak ◽  
Ronald E. Gress
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Graft Rejection ◽  
Marrow Transplant ◽  
Type I ◽  
Marrow Graft ◽  
Murine Bone Marrow ◽  
Cd8 Cells ◽  
Preparative Regimen

Abstract Donor CD8+ T cells capable of host reactivity inhibit marrow graft rejection, but also generate graft-versus-host disease (GVHD). To evaluate whether the Tc1- and Tc2-type subsets of CD8 cells might inhibit rejection without host reactivity, we established an F1 into-parent murine bone marrow transplant model. Donor Tc1 and Tc2 cells were generated that preferentially secreted type I or type II cytokines; both subsets possessed potent cytolytic function, and clonally deleted host-type allospecific precursor CTL in vitro. B6 hosts receiving 950 cGy irradiation did not reject the donor marrow (F1 chimerism of 78.6%; n = 10), whereas hosts receiving 650 cGy rejected the donor marrow (3.8% chimerism; n = 8). At 650 cGy irradiation, the addition of Tc2 cells to the F1 marrow resulted in extensive F1 chimerism (70.8%) in 8 of 8 recipients; in contrast, alloengraftment was not consistently observed in mice receiving Tc1 cells or unmanipulated CD8 cells. Furthermore, when the preparative regimen was further reduced to 600 cGy, only hosts receiving the Tc2-type cells did not reject the F1 marrow. We conclude that Tc2 cells potently inhibit marrow graft rejection without inducing an alloaggressive response and that non–host-reactive Tc2 cells therefore facilitate engraftment across genetic barriers with reduced GVHD.

scholarly journals Epitope Specificity of CD44 for Monoclonal Antibody–Dependent Facilitation of Marrow Engraftment in a Canine Model

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3494-3502 ◽  
Author(s):  
Brenda M. Sandmaier ◽  
Rainer Storb ◽  
Kelly L. Bennett ◽  
Frederick R. Appelbaum ◽  
Erlinda B. Santos
Keyword(s):  
Monoclonal Antibody ◽  
Graft Rejection ◽  
Marrow Transplantation ◽  
Canine Model ◽  
In Vivo Model ◽  
Preparative Regimen ◽  
Total Body ◽  
Hyaluronan Binding

Primary graft rejection after marrow transplantation occurs more frequently in patients receiving HLA-haploidentical compared with HLA-identical sibling transplants. Both human and experimental animal data suggest that the cells responsible for this phenomenon are either host natural killer (NK) cells, T cells, or both. To investigate the mechanisms of graft rejection, we have developed a canine model of marrow transplantation, which uses DLA-nonidentical unrelated donors in the absence of postgrafting immunosuppression. In this model most animals rejected their marrow grafts after a preparative regimen of 9.2 Gy total body irradiation (TBI). However, engraftment of DLA-nonidentical marrow can be facilitated when the recipients are pretreated with monoclonal antibody (MoAb) S5, which recognizes CD44. In this report, we extended these observations by first cloning the canine CD44 and, next, mapping the epitope recognized by S5, which was located in a region conserved among human and canine CD44 and was distinct from the hyaluronan binding domain. However, in vitro binding of S5 caused a conformational change in CD44, which allowed increased hyaluronan binding. Then, we reexamined the in vivo model of marrow transplantation and compared results with MoAb S5 to those with two other anti-CD44 MoAbs, IM7 and S3. Only MoAb S5 significantly increased the engraftment rate of DLA-nonidentical unrelated marrow, whereas the two other anti-CD44 MoAbs were ineffective. The enhanced in vivo effect was not related to differences in the MoAbs' avidities, since both S5 and IM7 had equivalent binding to CD44, but most likely related to the specific epitope that S5 recognizes. Thus, this study shows that the effect of the anti-CD44 MoAb S5 in facilitating engraftment is epitope specific and if one is to use an anti-CD44 to facilitate engraftment of marrow in humans, one cannot assume that any anti-CD44 would work.

scholarly journals Epitope Specificity of CD44 for Monoclonal Antibody–Dependent Facilitation of Marrow Engraftment in a Canine Model

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3494-3502 ◽  
Author(s):  
Brenda M. Sandmaier ◽  
Rainer Storb ◽  
Kelly L. Bennett ◽  
Frederick R. Appelbaum ◽  
Erlinda B. Santos
Keyword(s):  
Monoclonal Antibody ◽  
Graft Rejection ◽  
Marrow Transplantation ◽  
Canine Model ◽  
In Vivo Model ◽  
Preparative Regimen ◽  
Total Body ◽  
Hyaluronan Binding

Abstract Primary graft rejection after marrow transplantation occurs more frequently in patients receiving HLA-haploidentical compared with HLA-identical sibling transplants. Both human and experimental animal data suggest that the cells responsible for this phenomenon are either host natural killer (NK) cells, T cells, or both. To investigate the mechanisms of graft rejection, we have developed a canine model of marrow transplantation, which uses DLA-nonidentical unrelated donors in the absence of postgrafting immunosuppression. In this model most animals rejected their marrow grafts after a preparative regimen of 9.2 Gy total body irradiation (TBI). However, engraftment of DLA-nonidentical marrow can be facilitated when the recipients are pretreated with monoclonal antibody (MoAb) S5, which recognizes CD44. In this report, we extended these observations by first cloning the canine CD44 and, next, mapping the epitope recognized by S5, which was located in a region conserved among human and canine CD44 and was distinct from the hyaluronan binding domain. However, in vitro binding of S5 caused a conformational change in CD44, which allowed increased hyaluronan binding. Then, we reexamined the in vivo model of marrow transplantation and compared results with MoAb S5 to those with two other anti-CD44 MoAbs, IM7 and S3. Only MoAb S5 significantly increased the engraftment rate of DLA-nonidentical unrelated marrow, whereas the two other anti-CD44 MoAbs were ineffective. The enhanced in vivo effect was not related to differences in the MoAbs' avidities, since both S5 and IM7 had equivalent binding to CD44, but most likely related to the specific epitope that S5 recognizes. Thus, this study shows that the effect of the anti-CD44 MoAb S5 in facilitating engraftment is epitope specific and if one is to use an anti-CD44 to facilitate engraftment of marrow in humans, one cannot assume that any anti-CD44 would work.

Reduced MHC class II antigen expression on rat heart and kidney cells after in vitro exposure to longwave ultraviolet irradiation

1988 ◽  
Vol 19 (4) ◽  
pp. 273-278 ◽  
Author(s):  
Constanze Eichler ◽  
H. Oesterwitz ◽  
J. Kaden ◽  
W. Schneider ◽  
R. Schade ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Ultraviolet Irradiation ◽  
Rat Heart ◽  
Antigen Expression ◽  
Class Ii ◽  
Kidney Cells ◽  
In Vitro Exposure ◽  
Class Ii Antigen ◽  
Mhc Class Ii Antigen

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse
Keyword(s):  
High Purity ◽  
Time Course ◽  
Prothrombin Complex Concentrate ◽  
Degradation Products ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Albumin Infusion

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

The Development of Homologous (Canine/Anti-Canine) Antibodies in Dogs with Haemophilia A (Factor VIII Deficiency): A Ten-Year Longitudinal Study

1993 ◽  
Vol 69 (01) ◽  
pp. 021-024 ◽  
Author(s):  
Shawn Tinlin ◽  
Sandra Webster ◽  
Alan R Giles
Keyword(s):  
Factor Viii ◽  
Canine Model ◽  
Significant Inhibition ◽  
Human Condition ◽  
Haemophilia A ◽  
Variable Expression ◽  
The Family ◽  
Over Time

SummaryThe development of inhibitors to factor VIII in patients with haemophilia A remains as a serious complication of replacement therapy. An apparently analogous condition has been described in a canine model of haemophilia A (Giles et al., Blood 1984; 63:451). These animals and their relatives have now been followed for 10 years. The observation that the propensity for inhibitor development was not related to the ancestral factor VIII gene has been confirmed by the demonstration of vertical transmission through three generations of the segment of the family related to a normal (non-carrier) female that was introduced for breeding purposes. Haemophilic animals unrelated to this animal have not developed functionally significant factor VIII inhibitors despite intensive factor VIII replacement. Two animals have shown occasional laboratory evidence of factor VIII inhibition but this has not been translated into clinical significant inhibition in vivo as assessed by clinical response and F.VIII recovery and survival characteristics. Substantial heterogeneity of inhibitor expression both in vitro and in vivo has been observed between animals and in individual animals over time. Spontaneous loss of inhibitors has been observed without any therapies designed to induce tolerance, etc., being instituted. There is also phenotypic evidence of polyclonality of the immune response with variable expression over time in a given animal. These observations may have relevance to the human condition both in determining the pathogenetic factors involved in this condition and in highlighting the heterogeneity of its expression which suggests the need for caution in the interpretation of the outcome of interventions designed to modulate inhibitor activity.

RECONSTRUCTION OF DNA-REPAIR DEFICIENT XERODERMA PIGMENTOSUM SKIN IN VITRO: A MODEL TO STUDY HYPERSENSITIVITY TO UV LIGHT

2004 ◽  
Author(s):  
Françoise Bernerd ◽  
Daniel Asselineau ◽  
Mathilde Frechet ◽  
Alain Sarasin ◽  
Thierry Magnaldo
Keyword(s):  
Dna Repair ◽  
Xeroderma Pigmentosum ◽  
Uv Light
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