Disease relevance of Self Tolerance

• TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes [1].
• APECED: a monogenic autoimmune disease providing new clues to self-tolerance [2].
• BACKGROUND: Primary biliary cirrhosis (PBC) has an autoimmune aetiology, although little is known regarding the mechanisms of breakdown of self tolerance [3].
• These results support the hypothesis that CTLA-4 may play a role in regulating self-tolerance by the immune system and in the pathogenesis of autoimmune disorders such as Graves' disease [4].
• CONTEXT: Autoimmune thyroid diseases (AITD), comprising Graves' disease and autoimmune hypothyroidism, are characterized by loss of immunological self-tolerance to thyroid antigens [5].

High impact information on Self Tolerance

• Naturally occurring CD4+ regulatory T cells, the majority of which express CD25, are engaged in dominant control of self-reactive T cells, contributing to the maintenance of immunologic self-tolerance [6].
• It is now clear that all T cell recognition, including self-tolerance and allorecognition, involves both the MHC molecule and its associated peptide ligand [7].
• Until recently it has generally been assumed that self-tolerance and H-2-restricted specificity both reflect early T-cell contact with self H-2 determinants expressed on thymic epithelial cells [8].
• We report here a study designed to determine whether products of the major histocompatibility complex are involved in the induction of self tolerance; in particular, whether the induction of self tolerance in the mouse is H-2 restricted [9].
• This partial subversion of B cell self tolerance is likely to underlie the autoimmunity associated with BAFF overexpression [10].

Chemical compound and disease context of Self Tolerance

• Using a series of alanine-substituted peptides and additional appropriate synthetic peptides, it was demonstrated that the clones maintain self-tolerance because of their sensitivity to an asparagine to aspartic acid sequence difference between E. coli and HuHsp60 in the epitope-containing peptide [11].
• Induction of self-tolerance and enhanced stress protein synthesis in L-132 cells by cadmium chloride and by hyperthermia [12].

Biological context of Self Tolerance

• Interferon gamma plays a critical role in induced cell death of effector T cell: a possible third mechanism of self-tolerance [13].
• Thus, this study indicates the necessity of inhibiting SOCS1, an antigen presentation attenuator, to break self tolerance and induce effective antitumor responses [14].
• Apoptosis mediated by Fas ligand (FasL) interaction with Fas receptor plays a pivotal regulatory role in immune homeostasis, immune privilege, and self-tolerance [15].
• Transforming growth factor-beta (TGFbeta) is a potent growth inhibitor and inducer of apoptosis in B lymphocytes and is essential for immune regulation and maintenance of self-tolerance [16].
• Essential role of IkappaB kinase alpha in thymic organogenesis required for the establishment of self-tolerance [17].

Anatomical context of Self Tolerance

• MHC restriction, self-tolerance and the thymus [18].
• Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance [19].
• Our studies identify Stra13 as a key regulator of lymphocyte activation that is vital for maintenance of self-tolerance and for constraint of autoimmunity [20].
• We identified a tumor-associated cytotoxic T lymphocyte (CTL) epitope derived from the widely expressed human MDM2 oncoprotein and were able to bypass self-tolerance to this tumor antigen in HLA-A*0201 (A2.1) transgenic mice and by generating A2.1-negative, allo-A2.1-restricted human T lymphocytes [21].
• SOCS1 restricts dendritic cells' ability to break self tolerance and induce antitumor immunity by regulating IL-12 production and signaling [14].

Associations of Self Tolerance with chemical compounds

• The variability in the immunoreactive carrier/lipoate conjugates provides an experimental framework on which potential mechanisms for the breakdown of self-tolerance following exposure to xenobiotics can be investigated [22].
• This helps maintain self-tolerance in the face of TSH-increased gene products necessary for thyroid hormone formation [23].
• Bacterial motif DNA as an adjuvant for the breakdown of immune self-tolerance to pyruvate dehydrogenase complex [24].
• Paradoxically, cyclosporine A disrupts the immunologic homeostasis governing self-tolerance [25].
• Furthermore, we observed cross-resistance and self-tolerance with three seemingly unrelated stimuli (diamide, heat, and sodium arsenite) [26].

Gene context of Self Tolerance

• The role of complement in the maintenance of self-tolerance has been examined in two models: an immunoglobulin transgenic model of peripheral tolerance and a lupus-like murine model of CD95 (Fas) deficiency [27].
• We show that E2F2 is required for immunologic self-tolerance [28].
• These results add a novel enzymatic function for AIRE and suggest an indispensable role of the Ub proteasome pathway in the establishment of self-tolerance, in which AIRE is involved [29].
• Thus, the CD25(+)CD4(+) regulatory T cell population engaged in dominant self-tolerance may require CTLA-4 but not CD28 as a costimulatory molecule for its functional activation [30].
• We posit that their heightened expression of various costimulatory molecules, including CD80, CD106, I-A, and CD40, and their elevated production of various cytokines, including IL-12 and IL-1beta, may explain why Sle3-bearing DCs may be superior at breaching self tolerance [31].

Analytical, diagnostic and therapeutic context of Self Tolerance

• Tailoring p53-based cancer immunotherapy thus requires the interference with p53-specific self-tolerance and the induction of the entire repertoire of p53-reactive T lymphocytes [32].
• Systemic transforming growth factor-beta1 gene therapy induces Foxp3+ regulatory cells, restores self-tolerance, and facilitates regeneration of beta cell function in overtly diabetic nonobese diabetic mice [33].
• This emergence of self-recognition in the presence of M. tuberculosis Cpn10 could imply a breaking of self-tolerance in situations of infection or vaccination [34].

References