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

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.

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.

Oral Induction of Immunological Tolerance to Chromium in the Guinea Pig

1990 ◽  
Vol 69 (10) ◽  
pp. 1634-1639 ◽  
Author(s):  
K.J.J. Vreeburg ◽  
I.M.W. Van Hoogstraten ◽  
B.M.E. Von Blomberg ◽  
K. De Groot ◽  
R.J. Scheper
Keyword(s):  
Skin Testing ◽  
Tolerance Induction ◽  
Immunological Tolerance ◽  
Metal Alloys ◽  
High Dose ◽  
Allergic Reactions ◽  
Dose Frequency ◽  
Chromium Powder ◽  
Adverse Side Effects ◽  
Skin Contact

Metal alloys used in dentistry may elicit adverse side-effects. Contact allergic reactions to metals released from such alloys are among the most frequently encountered problems. In an earlier study, we observed that oral contacts with nickel or chromium salts did not sensitize, but rather decreased the risk of subsequent sensitization to these metals. In the present study, we focused on chromium allergy and extended our earlier observations by further dose-response studies. In addition, we compared different chromium valencies as to their potential oral tolerogenic effects. Development of immunological tolerance in chromium-fed guinea pigs was demonstrated by their inability to develop chromium hypersensitivity after a subsequent immunization attempt. For these studies, the techniques of immunization and skin testing were first improved. One feeding with a high dose of K2Cr2O7, (containing hexavalent chromium) was effective in full tolerance induction. In contrast, trivalent chromium (CrCl3) induced a distinctly lower degree of tolerance, whereas metallic chromium powder was not detectably tolerogenic after a limited number of feedings. Dose-frequency-response studies with K2Cr2O 7, showed that full tolerance could also be induced by an increase in the number of feedings with sub-optimal tolerogenic doses. The present results therefore support our hypothesis that long-lasting oral contact with chromium-releasing metal alloys may ultimately result in strong immune tolerance to this metal in subjects without previous skin contact with it. This view is further supported by recent insights into the unique tolerogenicity of oral, as compared with gastro-intestinal, allergenic contacts.

scholarly journals THE THYMUS AND RECOVERY FROM CYCLOPHOSPHAMIDE-INDUCED TOLERANCE TO SHEEP ERYTHROCYTES

1968 ◽  
Vol 128 (1) ◽  
pp. 35-46 ◽  
Author(s):  
Alan C. Aisenberg ◽  
Caroline Davis
Keyword(s):  
Proliferative Response ◽  
Tolerance Induction ◽  
Recovery Process ◽  
Immunological Tolerance ◽  
Base Line ◽  
Drug Injection ◽  
Sheep Erythrocytes ◽  
Lymphoid Depletion ◽  
Induced Tolerance ◽  
Specific Tolerance

Recovery from specific immunological tolerance to sheep erythrocytes induced with the drug cyclophosphamide was studied with the hemolytic plaque technique of Jerne. The base line plaque (19S antibody-forming cell of the unstimulated spleen) and the proliferative response to antigen, both of which had disappeared during tolerance induction, returned with the recovery of specific immunological reactivity. When cyclophosphamide is injected without sheep cells there is temporary immunological unreactivity and lymphoid depletion of the spleen, but specific tolerance is not induced. Recovery is largely complete at the end of 2 wk and does not require the participation of the thymus. When cyclophosphamide is injected together with sheep cells, 18 days after drug injection, tolerance is still complete. In nonthymectomized mice there is rapid recovery during the next 10 wk, followed by much slower restoration over the remaining 20–30 wk of observation. The entire recovery process evidently takes 40–50 wk. In thymectomized CBA mice only minimal recovery takes place in the first 10 wk and no further restoration occurs thereafter. Thymectomy performed 18 days after tolerance is induced, when tolerance is complete, is equally effective in preventing this recovery.

Aire regulates chromatin looping by evicting CTCF from domain boundaries and favoring accumulation of cohesin on superenhancers

2021 ◽  
Vol 118 (38) ◽  
pp. e2110991118
Author(s):  
Kushagra Bansal ◽  
Daniel A. Michelson ◽  
Ricardo N. Ramirez ◽  
Aaron D. Viny ◽  
Ross L. Levine ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Mechanistic Model ◽  
Tolerance Induction ◽  
Immunological Tolerance ◽  
Thymic Epithelial Cells ◽  
Structural Domain ◽  
Chromosome Conformation ◽  
Binding Factor ◽  
Domain Boundaries ◽  
Medullary Thymic Epithelial Cells

Aire controls immunological tolerance by driving promiscuous expression of a large swath of the genome in medullary thymic epithelial cells (mTECs). Its molecular mechanism remains enigmatic. High-resolution chromosome-conformation capture (Hi-C) experiments on ex vivo mTECs revealed Aire to have a widespread impact on higher-order chromatin structure, disfavoring architectural loops while favoring transcriptional loops. In the presence of Aire, cohesin complexes concentrated on superenhancers together with mediator complexes, while the CCCTC-binding factor (CTCF) was relatively depleted from structural domain boundaries. In particular, Aire associated with the cohesin loader, NIPBL, strengthening this factor’s affiliation with cohesin’s enzymatic subunits. mTEC transcripts up-regulated in the presence of Aire corresponded closely to those down-regulated in the absence of one of the cohesin subunits, SA-2. A mechanistic model incorporating these findings explains many of the unusual features of Aire’s impact on mTEC transcription, providing molecular insight into tolerance induction.

Induction of Immunological Tolerance to Islet Allografts

1996 ◽  
Vol 5 (1) ◽  
pp. 49-52 ◽  
Author(s):  
Aldo A. Rossini ◽  
David C. Parker ◽  
Nancy E. Phillips ◽  
Fiona H. Durie ◽  
Randolph J. Noelle ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
B Cells ◽  
Tolerance Induction ◽  
Immunological Tolerance ◽  
Splenic Lymphocytes ◽  
Allograft Survival ◽  
Spleen Cells ◽  
Islet Allografts ◽  
Dose Dependent

T-cell dependent activation of resting B cells involves the interaction of gp39 on T cells with its receptor, CD40, on B cells. We administered either a combination of T-cell-depleted splenic lymphocytes and anti-gp39 monoclonal antibody or antibody alone to establish islet allografts in mice without continuous immunosuppression. Fully allogeneic H-2q FVB islets were permanently accepted by chemically diabetic H-2b C57BL/6 mice provided that the recipients were pretreated with both T-cell-depleted donor spleen cells and anti-gp39 antibody. Antibody alone was less effective in prolonging allograft survival, but we did observe that anti-gp39 mAb alone can exert an independent, primary effect on islet allograft survival that was dose dependent. Targeting gp39, in combination with lymphocyte transfusion, might prove suitable for tolerance induction and allotransplantation without immunosuppression.

scholarly journals Induction of immunological tolerance requires that the B cells can respond to the polyclonal B-cell-activating properties of the thymus-independent antigens.

1977 ◽  
Vol 146 (1) ◽  
pp. 308-312 ◽  
Author(s):  
C Fernandez ◽  
G Möller
Keyword(s):  
B Cells ◽  
B Cell ◽  
Tolerance Induction ◽  
Immunological Tolerance ◽  
Spleen Cells ◽  
Normal Cells ◽  
Purified Protein Derivative ◽  
High Affinity

Mice were rendered specifically tolerant to the fluorescein isothiocyanatedextran (FITC) epitope by injection of FITC-dextran B512. Their spleen cells were removed at various times and cultivated in vitro with different polyclonal B-cell activators, such as lipopolysaccharide (LPS), purified protein derivative of tuberculin, and native dextran. LPS caused the appearance of high affinity anti-FITC plaque-forming cells to an equal extent with cells from untreated and tolerant animals, whereas native dextran failed to activate cells from tolerant mice, although it was a potent activator of normal cells. It was concluded that tolerance induction only affects those B cells that could respond to the polyclonal B-cell-activating properties of the tolerogen, but not other B cells having an identical set of Ig receptors directed against the tolerogen.

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.

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