scholarly journals Xenotransplantation and tolerance

2001 ◽  
Vol 356 (1409) ◽  
pp. 749-758 ◽  
Author(s):  
Benjamin Samstein ◽  
Jeffrey L. Piatt
Keyword(s):  
Tolerance Induction ◽  
Suppressor Cells ◽  
Immunological Tolerance ◽  
Humoral Rejection ◽  
B Cell Tolerance ◽  
Clonal Deletion ◽  
Porcine Organs ◽  
Veto Cells ◽  
Cellular Rejection ◽  
Xenoreactive Antibodies

The application of xenotransplantation faces daunting immunological hurdles, some of which might be overcome with the induction of tolerance. Porcine organs transplanted into primates are subject to several types of rejection responses. Hyperacute rejection mediated by naturally occurring xenoreactive antibodies and complement can be overcome without tolerance. Acute vascular rejection and cellular rejection, however, may present important opportunities for immunological tolerance, and humoral rejection might be approached by various mechanisms including (i) clonal deletion, (ii) anergy, (iii) immune deviation, (iv) induction of immunoregulatory or suppressor cells, or (v) veto cells. B-cell tolerance, useful for preventing humoral rejection, might be approached through clonal anergy. It remains to be determined, however, whether tolerance induction is required for xenotransplantation and by which means the various mechanisms of tolerance can be applied in the setting of xenotransplantation. Regardless, the study of tolerance will surely expand understanding of the physiology and pathophysiology of the immune system.

scholarly journals Liver-expressed Igκ superantigen induces tolerance of polyclonal B cells by clonal deletion not κ to λ receptor editing

2011 ◽  
Vol 208 (3) ◽  
pp. 617-629 ◽  
Author(s):  
Takayuki Ota ◽  
Miyo Ota ◽  
Bao Hoa Duong ◽  
Amanda L. Gavin ◽  
David Nemazee
Keyword(s):  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Tolerance Induction ◽  
Cell Receptor ◽  
Mature Stage ◽  
Receptor Editing ◽  
Cell Tolerance ◽  
B Cell Tolerance ◽  
Clonal Deletion

Little is know about the nature of peripheral B cell tolerance or how it may vary in distinct lineages. Although autoantibody transgenic studies indicate that anergy and apoptosis are involved, some studies claim that receptor editing occurs. To model peripheral B cell tolerance in a normal, polyclonal immune system, we generated transgenic mice expressing an Igκ–light chain–reactive superantigen targeted to the plasma membrane of hepatocytes (pAlb mice). In contrast to mice expressing κ superantigen ubiquitously, in which κ cells edit efficiently to λ, in pAlb mice, κ B cells underwent clonal deletion. Their κ cells failed to populate lymph nodes, and the remaining splenic κ cells were anergic, arrested at a semi-mature stage without undergoing receptor editing. In the liver, κ cells recognized superantigen, down-regulated surface Ig, and expressed active caspase 3, suggesting ongoing apoptosis at the site of B cell receptor ligand expression. Some, apparently mature, κ B1 and follicular B cells persisted in the peritoneum. BAFF (B cell–activating factor belonging to the tumor necrosis factor family) overexpression rescued splenic κ B cell maturation and allowed κ cells to populate lymph nodes. Our model facilitates analysis of tissue-specific autoimmunity, tolerance, and apoptosis in a polyclonal B cell population. The results suggest that deletion, not editing, is the major irreversible pathway of tolerance induction among peripheral B cells.

scholarly journals Tolerance induction during ontogeny. I. Presence of active suppression in mice rendered tolerant to human gamma-globulin in utero correlates with the breakdown of the tolerant state.

1979 ◽  
Vol 149 (5) ◽  
pp. 1134-1151 ◽  
Author(s):  
C A Waters ◽  
L M Pilarski ◽  
T G Wegmann ◽  
E Diener
Keyword(s):  
Gamma Globulin ◽  
Tolerance Induction ◽  
Suppressor Cells ◽  
In Utero ◽  
Cell Tolerance ◽  
B Cell Tolerance ◽  
Active Suppression ◽  
Self Tolerance ◽  
Human Gamma Globulin ◽  
Tolerant State

A specific state of T- and B-cell tolerance to human gamma-globulin (HGG) was induced in utero by intravenous administration of the deaggregated antigen to pregnant BALB/cCr mice. Tolerance persisted in the offspring until the 12th-wk of age and then began to gradually disappear. Suppressor cells could only be found when responsiveness to HGG ultimately appeared in the in utero-treated animals but not when they were completely unresponsives. In contrast, HGG-specific suppressors found in animals made unresponsive to HGG as adults appear to be associated with either the establishment and/or maintenance of the unresponsive state. To the extent that these experiments are consistent with natural self-tolerance to a serum protein, we conclude that active suppression is not a prerequisite from maintenance of unresponsiveness to self.

scholarly journals STUDIES ON CYCLOPHOSPHAMIDE-INDUCED TOLERANCE TO SHEEP ERYTHROCYTES

1967 ◽  
Vol 125 (5) ◽  
pp. 833-845 ◽  
Author(s):  
Alan C. Aisenberg
Keyword(s):  
Tolerance Induction ◽  
Acid Synthesis ◽  
Progressive Increase ◽  
Immunological Tolerance ◽  
Receptor Sites ◽  
Deoxyribonucleic Acid Synthesis ◽  
Isotopic Methods ◽  
Radiation Induced ◽  
Immunological Suppression ◽  
Induced Tolerance

Complete immunological tolerance to sheep cells can be induced in mice when cyclophosphamide is injected together with sheep cells or up to 72 hr before or 48 hr after the antigen. As is true for radiation-induced immune suppression, the drug is most effective when given in the 24 hr prior to antigen. Complete cyclophosphamide-induced immunological suppression requires large doses of sheep cells (6.2 x 109 cells), presumably to enable antigen to reach sequestered receptor sites. The cyclophosphamide tolerance system has been analyzed with the Jerne technique to determine plaque-forming cells and with isotopic methods to measure rates of nucleic acid synthesis. This drug suppression has been found to consist of two components. The first is nonspecific injury to the lymphoid system caused by the cytotoxic drug and is related to the proportion of spleen cells killed. The second is antigen-specific immunological tolerance and appears to correlate with profound depression of deoxyribonucleic acid synthesis in the surviving cells. This tolerance is thought to be most consistent with a mechanism in which antigenic stimulation in the presence of cyclophosphamide-inhibited DNA synthesis and mitosis leads to the elimination or death of the specific immunological clone. Tolerance induction with cyclophosphamide is associated with loss of the 19S hemolysin plaques which are seen in nonstimulated mouse spleen, implicating these cells in immune responsiveness. The ability to induce tolerance is lost on the 3rd postantigen day at the end of a 24-hr period in which 19S cells have increased 8-fold and 7S cells 200-fold. The data suggest that loss of sensitivity is due to the emergence on day 3 of drug-resistant plaque-forming cells, particularly those of the 19S variety. In the succeeding days after antigen injection there is a progressive increase in the resistance of plaque-forming cells to cyclophosphamide administration.

Possible Roles of Suppressor Cells in Immunological Tolerance

1975 ◽  
Vol 26 (1) ◽  
pp. 186-205
Author(s):  
William O. Weigle ◽  
Donna G. Sieckmann ◽  
Michael V. Doyle ◽  
Jacques M. Chiller
Keyword(s):  
Suppressor Cells ◽  
Immunological Tolerance

Failure of Neonatal B-Cell Tolerance Induction by ABO-Incompatible Kidney Grafts in Piglets

2013 ◽  
Vol 96 (6) ◽  
pp. 519-528 ◽  
Author(s):  
Mylvaganam Jeyakanthan ◽  
Xianpei Zhou ◽  
KeSheng Tao ◽  
Michael Mengel ◽  
Ray V. Rajotte ◽  
...  
Keyword(s):  
B Cell ◽  
Tolerance Induction ◽  
Cell Tolerance ◽  
B Cell Tolerance

Innowacyjna metoda prowadzenia ITI za pomocą preparatu czynnika VIII z frakcją Fc u pacjentów z hemofilią A z obecnością inhibitora czynnika VIII – przegląd literaturowy

2018 ◽  
Vol 22 (3) ◽  
Author(s):  
Maciej Trzaska ◽  
Marek Karwacki ◽  
Paweł Łaguna ◽  
Michał Matysiak
Keyword(s):  
Factor Viii ◽  
Tolerance Induction ◽  
Standard Of Care ◽  
Preliminary Evidence ◽  
Immunological Tolerance ◽  
Therapeutic Benefit ◽  
High Titre ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
First Time

Eradication of factor VIII inhibitors using Immune tolerance induction (ITI) treatment is the standard of care for severe haemophilia A patients presenting with factor VIII inhibitors, but is not always effective. A description of the potential immunological tolerance effect of the IgG Fc domain of recombinant factor VIII Fc fusion protein (rFVIIIFc), as well as published experience with rFVIIIFc for ITI in patients with severe haemophilia A and high-titre inhibitors. Review of published literature describing cases of ITI with rFVIIIFc in patients with severe haemophilia A and high-titre inhibitors between November 2015 and June 2018. Four publications has been found. Of 56 patients with haemophilia A who presented with FVIII inhibitors, 28 achieved a negative Bethesda titre (< 0.6) after ITI treatment using rFVIIIFc. Additional patients continued on rFVIIIFc ITI at the time of publication, while a few were reported to have switched to bypass therapy alone or other factors . For those still undergoing ITI, longer follow-up is needed to determine final outcomes. No adverse events were reported. Based on literature review, preliminary evidence of FVIIIFc use in high risk, first-time ITI suggests rapid time to tolerization. For rescue ITI, rFVIIIFc showed therapeutic benefit in some patients who previously failed ITI. These findings give hope but highlight the need for further evaluation in ongoing clinical trials.

Partial Immunological Tolerance Induction with Extracorporeal Photopheresis

2018 ◽  
Vol 102 ◽  
pp. S261
Author(s):  
Aleksei Zulkarnaev ◽  
Andrey Vatazin ◽  
Alexander Kildushevsky ◽  
Veronika Fedulkina ◽  
Alexander Faenko
Keyword(s):  
Tolerance Induction ◽  
Immunological Tolerance ◽  
Extracorporeal Photopheresis
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