Disease relevance of Immune Tolerance

• Furthermore, transgenic B7-H1 expression broke immune tolerance, as some of the mice spontaneously developed T cell-dependent autoimmune diabetes [1].
• Here, we report that overexpression of MYC, as found in many lymphomas, can break immune tolerance [2].
• Long-term induction of immune tolerance after blockade of CD40-CD40L interaction in a mouse model of hemophilia A [3].
• Depletion of NK1.1+ LAL prevented immune tolerance induction in the experimental colitis model [4].
• Thus, diminished expression and function of T cell TLR is a novel mechanism underlying T cell immune tolerance in lymphatic filariasis [5].

High impact information on Immune Tolerance

• The protective effect may be explained by higher levels of class III VNTR-associated INS mRNA in thymus such that elevated levels of preproinsulin protein enhance immune tolerance to preproinsulin, a key autoantigen in type 1 diabetes pathogenesis [6].
• Insulin was detected in all thymus tissues examined and class III VNTR alleles were associated with 2- to 3-fold higher INS mRNA levels than class I. We therefore propose higher levels of thymic INS expression, facilitating immune tolerance induction, as a mechanism for the dominant protective effect of class III alleles [7].
• A critical role for Stat3 signaling in immune tolerance [8].
• Regulatory T cells (T(reg) cells) expressing the forkhead family transcription factor Foxp3 are critical mediators of dominant immune tolerance to self [9].
• If the assumption that immune tolerance determines the range of anti-Gal specificity is correct, then anti-Gal from individuals lacking the B antigen (A and O blood types) would be expected to interact with both Gal alpha 1----3Gal and Gal alpha 1----3(Fuc alpha 1----2)Gal epitopes [10].

Chemical compound and disease context of Immune Tolerance

• A factor VIII-deficient knockout mouse was used as a model for severe hemophilia A to characterize the immune response to recombinant human factor VIII (fVIII) and to study new approaches for induction of immune tolerance to fVIII [3].
• Immunization with surface antigen vaccine alone and after treatment with 1-(2-fluoro-5-methyl-beta-L-arabinofuranosyl)-uracil (L-FMAU) breaks humoral and cell-mediated immune tolerance in chronic woodchuck hepatitis virus infection [11].
• We aimed to induce experimental immune tolerance to vascularized heart allograft using a suicide gene allowing selective elimination of dividing T cells expressing Herpes simplex virus type 1 thymidine kinase upon ganciclovir administration [12].
• Complete remission and possible immune tolerance after multidrug combination chemotherapy for cyclosporine-related lymphoma in a renal transplant recipient with acute pancreatitis [13].
• The immune tolerance in a 12-year-old haemophilia A patient was carried out at the Faculty of Medicine, Ramathibodi Hospital, Bangkok in 1998 [14].

Biological context of Immune Tolerance

• The HLA-G molecule plays an important role in immune tolerance, protecting the fetus from maternal immune attack, and probably contributes to graft tolerance and tumor escape from the host immune system [15].
• This study provides evidence vindicating the first hypothesis; namely, that intravascular prenatal administration of an adenoviral vector carrying the human factor IX (hFIX) transgene can induce immune tolerance of the transgenic protein [16].
• Accommodation of the fetoplacental unit in human pregnancy requires maternal immune tolerance to this "semiallograft". Local antiplacental immunity is modified by synthesis of uncommon histocompatibility Ags (e.g., HLA-G), growth factors, and cytokines by the placenta [17].
• We conclude that immune tolerance to bone marrow transplants involves clonal deletion, and tolerance to heart allografts in this model also involves regulatory CD1-reactive NK T cells [18].
• These findings suggest that FasL expressed by fetal trophoblast cells can induce apoptosis in activated lymphocytes there by providing a mechanism for maternal immune tolerance to the fetus [19].

Anatomical context of Immune Tolerance

• To test the hypothesis that chronic stimulation of T cells with a weak agonistic antigen will generate regulatory T cells and immune tolerance, a study reported in this issue employed the redesign of a minor histocompatibility antigen [20].
• Myelin/oligodendrocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice [21].
• The interaction between lymphocytes and the resident hepatic macrophage, the Kupffer cell (KC), is relevant to the phenomenon of immune tolerance to Ags entering the liver [22].
• Dendritic cell differentiation and immune tolerance to insulin-related peptides in Igf2-deficient mice [23].
• These results suggest that hCG may be a link in the development of peritrophoblastic immune tolerance and may facilitate the trophoblast invasion by regulating proapoptotic molecules such as FasL in endometrial cells [24].

Associations of Immune Tolerance with chemical compounds

• Covalent modification as a mechanism for the breakdown of immune tolerance to pyruvate dehydrogenase complex in the mouse [25].
• Our findings suggest that one mechanism by which an increased number of immune suppressive Gr-1+ cells can induce T cell unresponsiveness or immune tolerance in tumor hosts could be through peroxynitrite production upon primary T cell activation [26].
• CONCLUSIONS: Blockade of CD40 pathway with anti-CD40L mAb potentiates the tolerogenic potential of DC-CTLA4Ig and enhances the induction of antigen-specific immune tolerance more effectively [27].
• The results have established that specific immune tolerance to poison ivy urushiol is induced following 2 epicutaneous applications of the PDC analog [28].
• Production of indoleamine 2,3-dioxygenase (IDO) by tumor cells, leading to tryptophan depletion and production of immunosuppressive metabolites, may facilitate immune tolerance of cancer [29].

Gene context of Immune Tolerance

• To determine whether anti-CD40L treatment induces long-term immune tolerance, mice were rechallenged 3 times with fVIII alone [3].
• In concordance with its role in immune tolerance, AIRE is most strongly expressed in thymic epithelial cells and in cells of monocytic-dendritic lineage [30].
• Ultraviolet light-induced immune tolerance is mediated via the Fas/Fas-ligand system [31].
• FOXP3 is playing an essential role for T regulatory cells and is involved in the molecular mechanisms controlling immune tolerance [32].
• Expression of H2-Bl was previously detected only at the maternal/fetal interface, where it was proposed to induce immune tolerance via interactions with CD94/NKG2A receptors [33].

Analytical, diagnostic and therapeutic context of Immune Tolerance

• These findings suggest that under the experimental conditions used, 3H1-DC vaccination was better than CEA-DC vaccination in breaking immune tolerance to CEA and inducing protective antitumor immune responses in this murine model transgenic for human CEA [34].
• Fas ligand as a tool for immunosuppression and generation of immune tolerance [35].
• Antigen-driven peripheral immune tolerance: suppression of experimental autoimmmune encephalomyelitis and collagen-induced arthritis by aerosol administration of myelin basic protein or type II collagen [36].
• Immune tolerance induced by donor antigen and cyclophosphamide in rat fetal small bowel transplantation [37].
• Experimental studies performed in rat kidney transplantation showed that treatment with 15-deoxyspergualin (15-DOS) for 14 days after grafting may induce both permanent graft function and specific immune tolerance [38].

References