Self-tolerance

Breaking Self-Tolerance Leads to Antoimmnne Disease... 

Autoimmune Disease. Figure 1 Mechanisms of self tolerance. DC, dendritic (antigen presenting) cell T, T-lymphocyte Th, T helper lymphocyte Treg, T regulatory lymphocyte. For details see text. 

T- or B-lymphocytes which react with autoantigens. In healthy individuals kept under control by the mechanisms of self tolerance. 

The Th-1 /Th-2 paradigma forms a core mechanism regulating the nature of an immune response. More recently, this concept was further developed by identifying Th-subsets with predominantly suppressing properties, T-regulatory cells (Treg). These cells also play a major role in keeping those cells at rest, which have escaped central tolerance (peripheral self tolerance). 

Goodnow CC (2001) Pathways for self-tolerance and the treatment of autoimmune diseases. Lancet 357 2115-2121... 

Lavasani S, Dzhambazov B, Andersson M (2007) Monoclonal antibody against T-cell receptor alphabeta induces self-tolerance in chronic experimental autoimmune encephalomyelitis. Scand J Immunol 65 39-47... 

Autoimmune diseases in which immunological self-tolerance breaks down and the immune system launches an attack on self-antigens. 

Sakaguchi, S. et al., Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases, J. Immunol. 155, 1151-1164, 1995. 

Goodnow, C.C. et al., Cellular and genetic mechanisms of self tolerance and autoimmunity, Nature, 435, 590, 2005. 

Itoh M, Takahashi T, Sakaguchi N, Kuniyasu Y, Shimizu J, Otsuka F, Sakaguchi S Thymus and autoimmunity production ofCD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J Immunol 1999 162 5317-5326. 

SakaguchiS, Sakaguchi N Regulatory T cells in immunologic self-tolerance and autoimmune disease. Int Rev Immunol 2005 24 211-226. 

In the last decade there has been increasing interest in the scientific community in T-cell-mediated immunosuppression or regulation as a mechanism of self-tolerance and immune regulation. To date. 

Besides ensuring self-tolerance, different types of Tregs actively participate in immune responses. 

Shevach EM From vanilla to 28 flavors multiple varieties ofT regulatory cells. Immunity 2006 25 195-201. Sakaguchi S, Fukuma K, Kuribayashi K, Masuda T Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance deficit of a T cell subset as a possible cause of autoimmune disease. J Exp Med 1985 161 72-85. 

Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol 2002 3 135-142. 

Schwartz R Natural regulatory T cells and self-tolerance. Nat Immunol 2005 6 327-330. 

However, according to the fifth sentence of paragraph 2, in this instance, the state is referred to as self-tolerance. 

In conclusion, these results demonstrate that affinity and specificity of A2.1-restricted TCRs, selected in Tg mice by circumventing self-tolerance to universal hdm2- and wt p53-derived CTL epitopes, can be successfully delivered into human T lymphocytes. This, however, is precisely the molecular requirement to rescue the human T cell repertoire with high-affinity leukemia and tumor-reactive TCRs that have been lost due to the establishment of antigen-specific self-tolerance [13, 14]. 

V6. Van Rarijs, L., and Abbas, A. K., Homeostasis and self-tolerance in the immune system Turning lymphocytes off. Science 280, 243-248 (1998). 

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