Abstract:
:Recent elucidation of the role of central tolerance in preventing organ-specific autoimmunity has changed our concepts of self/nonself discrimination. This paradigmatic shift is largely attributable to the discovery of promiscuous expression of tissue-restricted self-antigens (TRAs) by medullary thymic epithelial cells (mTECs). TRA expression in mTECs mirrors virtually all tissues of the body, irrespective of developmental or spatio-temporal expression patterns. This review summarizes current knowledge on the cellular and molecular regulation of TRA expression in mTECs, outlines relevant mechanisms of antigen presentation and modes of tolerance induction, and discusses implications for the pathogenesis of autoimmune diseases and other biological processes such as fertility, pregnancy, puberty, and tumor defense.
journal_name
Annu Rev Immunoljournal_title
Annual review of immunologyauthors
Kyewski B,Klein Ldoi
10.1146/annurev.immunol.23.021704.115601subject
Has Abstractpub_date
2006-01-01 00:00:00pages
571-606eissn
0732-0582issn
1545-3278journal_volume
24pub_type
杂志文章,评审abstract::Over a decade has passed since the identification of the human immunodeficiency virus (HIV) as the causative agent of AIDS. During this time, HIV has been extensively characterized, and a variety of vaccine constructs and strategies have been explored. For the most part, these have been driven by successes of the past...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.12.040194.004423
更新日期:1994-01-01 00:00:00
abstract::Stressors ranging from nutrient deprivation to immune signaling can induce the degradation of cytoplasmic material by a process known as autophagy. Increasingly, research on autophagy has begun to focus on its role in inflammation and the immune response. Autophagy acts as an immune effector that mediates pathogen cle...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-020711-074948
更新日期:2012-01-01 00:00:00
abstract::In light of recent data showing that both helper and cytotoxic T cells can detect even a single molecule of an agonist peptide-MHC, alphabeta T cells are clearly a type of sensory cell, comparable to any in the nervous system. In addition, endogenous (self) peptides bound to MHCs are not just important for thymic sele...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.24.021605.090600
更新日期:2007-01-01 00:00:00
abstract::T cell activation leads to dramatic shifts in cell metabolism to protect against pathogens and to orchestrate the action of other immune cells. Quiescent T cells require predominantly ATP-generating processes, whereas proliferating effector T cells require high metabolic flux through growth-promoting pathways. Further...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-032712-095956
更新日期:2013-01-01 00:00:00
abstract::The Class 2 alpha-helical cytokines consist of interleukin-10 (IL-10), IL-19, IL-20, IL-22, IL-24 (Mda-7), and IL-26, interferons (IFN-alpha, -beta, -epsilon, -kappa, -omega, -delta, -tau, and -gamma) and interferon-like molecules (limitin, IL-28A, IL-28B, and IL-29). The interaction of these cytokines with their spec...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.22.012703.104622
更新日期:2004-01-01 00:00:00
abstract::Our understanding of the X-linked lymphoproliferative syndrome (XLP) has advanced significantly in the last two years. The gene that is altered in the condition (SAP/SH2D1A) has been cloned and its protein crystal structure solved. At least two sets of target molecules for this small SH2 domain-containing protein have...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.19.1.657
更新日期:2001-01-01 00:00:00
abstract::NK cells sit at the crossroads of innate and adaptive immunity and help coordinate tumor immunosurveillance and the immune response against pathogens. Balancing signals to NK cell precursors is crucial for their early development, when transcription factors compete to specify the different lymphocyte subsets. Despite ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.24.021605.090700
更新日期:2006-01-01 00:00:00
abstract::While still incomplete, the first data concerning the biochemistry of T cell receptor-ligand interactions in cell-free systems seem to have considerable predictive value regarding whether a T cell response is strong or weak or suppressive. This data will help considerably in elucidating the mechanisms behind T cell re...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.16.1.523
更新日期:1998-01-01 00:00:00
abstract::The epithelial architecture of the thymus fosters growth, differentiation, and T cell receptor repertoire selection of large numbers of immature T cells that continuously feed the mature peripheral T cell pool. Failure to build or to maintain a proper thymus structure can lead to defects ranging from immunodeficiency ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.26.021607.090408
更新日期:2008-01-01 00:00:00
abstract::The signaling lymphocyte activation molecule (SLAM)-associated protein, SAP, was first identified as the protein affected in most cases of X-linked lymphoproliferative (XLP) syndrome, a rare genetic disorder characterized by abnormal responses to Epstein-Barr virus infection, lymphoproliferative syndromes, and dysgamm...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-030409-101302
更新日期:2011-01-01 00:00:00
abstract::Autoimmunity and the pathogenesis of autoimmune diseases were a major focus of the Walter and Eliza Hall Institute, where I started my research career. After my initial studies on immune cell culture and immune regulation, I returned to an analysis of the pathogenesis of human autoimmunity in London. Linking upregulat...
journal_title:Annual review of immunology
pub_type: 传,历史文章,杂志文章
doi:10.1146/annurev-immunol-082708-100732
更新日期:2009-01-01 00:00:00
abstract::The discovery of new functions for the original B7 family members, together with the identification of additional B7 and CD28 family members, have revealed new ways in which the B7:CD28 family regulates T cell activation and tolerance. B7-1/B7-2:CD28 interactions not only promote initial T cell activation but also reg...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.23.021704.115611
更新日期:2005-01-01 00:00:00
abstract::The immune system is composed of single cells, and its function is entirely dependent on the capacity of these cells to traffic, localize within tissues, and interact with each other in a precisely coordinated fashion. There is growing evidence that the large families of chemokines and chemokine receptors provide a fl...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.18.1.593
更新日期:2000-01-01 00:00:00
abstract::Licensed vaccines against viral diseases generate antibodies that neutralize the infecting virus and protect against infection or disease. Similarly, an effective vaccine against HIV-1 will likely need to induce antibodies that prevent initial infection of host cells or that limit early events of viral dissemination. ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-030409-101256
更新日期:2010-01-01 00:00:00
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journal_title:Annual review of immunology
pub_type: 杂志文章
doi:10.1146/annurev-immunol-100819-121537
更新日期:2020-04-26 00:00:00
abstract::Analysis of cytokine mRNA and protein in rheumatoid arthritis tissue revealed that many proinflammatory cytokines such as TNF alpha, IL-1, IL-6, GM-CSF, and chemokines such as IL-8 are abundant in all patients regardless of therapy. This is compensated to some degree by the increased production of anti-inflammatory cy...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.14.1.397
更新日期:1996-01-01 00:00:00
abstract::CD45 is one of the most abundant leukocyte cell surface glycoproteins and is expressed exclusively upon cells of the hematopoietic system. Different isoforms of CD45 are generated by alternative splicing and are expressed in cell type-specific patterns on functional subpopulations of lymphocytes. In a major advance, C...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.12.040194.000505
更新日期:1994-01-01 00:00:00
abstract::In humans and experimental animals the presence of bacterial lipopolysaccharide (endotoxin, LPS) signals the presence of gram-negative bacteria. Recognition of LPS triggers gene induction by myeloid and nonmyeloid lineage cells. These inducible genes encode proteins that include cytokines, adhesive proteins, and enzym...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.13.040195.002253
更新日期:1995-01-01 00:00:00
abstract::The bare lymphocyte syndrome (BLS) is a hereditary immunodeficiency resulting from the absence of major histocompatibility complex class II (MHCII) expression. Considering the central role of MHCII molecules in the development and activation of CD4(+) T cells, it is not surprising that the immune system of the patient...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.19.1.331
更新日期:2001-01-01 00:00:00
abstract::Neutrophils provide the first line of defense of the innate immune system by phagocytosing, killing, and digesting bacteria and fungi. Killing was previously believed to be accomplished by oxygen free radicals and other reactive oxygen species generated by the NADPH oxidase, and by oxidized halides produced by myelope...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.23.021704.115653
更新日期:2005-01-01 00:00:00
abstract::B lymphopoiesis is regulated by multiple signals from stromal cell contact, soluble cytokines, antigen, and T helper cells. In vitro and biochemical experiments have implicated tyrosine kinases as key components of many of these signaling pathways. Genetic analysis of the role of these tyrosine kinases has been facili...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.14.1.131
更新日期:1996-01-01 00:00:00
abstract::The introduction of cloned genes into the germline of mice has been proven to be a powerful tool to investigate the role of the respective gene products within the immune system. Here we summarize the transgenic mouse models that have been established with major histocompatibility complex (MHC) class-I genes. Foreign ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.09.040191.001501
更新日期:1991-01-01 00:00:00
abstract::The discovery of tissue-resident innate lymphoid cell populations effecting different forms of type 1, 2, and 3 immunity; tissue repair; and immune regulation has transformed our understanding of mucosal immunity and allergy. The emerging complexity of these populations along with compounding issues of redundancy and ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-041015-055549
更新日期:2016-05-20 00:00:00
abstract::The nonobese diabetic (NOD) mouse is a model of human autoimmune insulin-dependent diabetes mellitus. The NOD mouse also serves as a model for studying complex polygenic diseases because at least fourteen different loci are linked to disease development. The first Idd locus recognized, Idd1, is linked to the major his...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.13.040195.001143
更新日期:1995-01-01 00:00:00
abstract::MHC class I molecules are peptide receptors of stringent specificity which however still allow millions of different ligands. This is achieved by the following specificity characteristics summarized as allele specific peptide motifs: Peptides are of defined length, depending on the class I allele (either 8 or 9 residu...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.11.040193.001241
更新日期:1993-01-01 00:00:00
abstract::T helper cell differentiation occurs in the context of the extracellular cytokine milieu evoked by diverse microbes and other pathogenic stimuli along with T cell receptor stimulation. The culmination of these signals results in specification of T helper lineages, which occurs through the combinatorial action of multi...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-020711-075058
更新日期:2012-01-01 00:00:00
abstract::T and B cells share a common somatic gene rearrangement mechanism for assembling the genes that code for their antigen receptors; they also have developmental pathways with many parallels. Shared usage of basic helix-loop-helix E proteins as transcriptional drivers underlies these common features. However, the transcr...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-032712-100024
更新日期:2014-01-01 00:00:00
abstract::During alphabeta T cell development, cells diverge into alternate CD4 helper and CD8(+) cytotoxic T cell lineages. The precise correlation between a T cell's CD8 and CD4 choice and its TCR specificity to class I or class II MHC was noted more than 20 years ago, and establishing the underlying mechanism has remained a ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.25.022106.141715
更新日期:2010-01-01 00:00:00
abstract::A reciprocal regulation exists between the central nervous and immune systems through which the CNS signals the immune system via hormonal and neuronal pathways and the immune system signals the CNS through cytokines. The primary hormonal pathway by which the CNS regulates the immune system is the hypothalamic-pituita...
journal_title:Annual review of immunology
pub_type: 杂志文章
doi:10.1146/annurev.immunol.20.082401.104914
更新日期:2002-01-01 00:00:00
abstract::It is possible to create mice in which a planned alteration has been introduced at a specific locus in the genome. The planned alteration is first introduced into the genome of mouse embryonic stem (ES) cells in tissue culture. This is accomplished by homologous recombination between the targeted genomic locus and DNA...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.10.040192.003421
更新日期:1992-01-01 00:00:00