Abstract：
:T-cell development is a highly coordinated process that depends on interactions between thymocytes, thymic epithelium, and bone marrow (BM)-derived dendritic cells (DCs). Before entering the peripheral T-cell pool, thymocytes are subject to negative selection, a process that eliminates (or deletes) T cells with high affinity toward self-antigens and therefore promotes self-tolerance. These self-antigens include those that are broadly expressed ubiquitous antigens and those whose expression is restricted to a few tissues, tissue-specific antigens (TSAs). Expression of TSAs in the thymus is mostly a property of medullary thymic epithelial cells (mTECs), and because these cells may be less capable than BM-derived DCs at mediating negative selection to ubiquitous antigens, we investigated the roles of both of these cell types in tolerance to TSAs. Here, we review our studies in which we found that mTECs were competent mediators of negative selection to a subset of TSA-reactive T cells, while thymic DCs extend the range of TSA-reactive T cells that undergo negative selection by capturing TSAs from mTECs. In addition, we recently investigated the efficiency of central tolerance to TSA during ontogeny, and we report that this process was less efficient in neonates than adult animals.
journal_name
Immunol Revjournal_title
Immunological reviewsauthors
Gallegos AM,Bevan MJdoi
10.1111/j.0105-2896.2006.00348.xkeywords:
subject
Has Abstractpub_date
2006-02-01 00:00:00pages
290-6eissn
0105-2896issn
1600-065Xpii
IMR348journal_volume
209pub_type
杂志文章,评审abstract：:Self-tolerance is achieved by deleting or regulating self-reactive lymphocytes at a series of cellular checkpoints placed at many points along the developmental pathways to plasma cells and effector T cells. At each checkpoint, what are the molecular pathways that determine whether a lymphocyte remains quiescent, begi...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2000.00614.x
更新日期：2000-08-01 00:00:00
abstract：:In spite of some remarkable progress in our understanding of the immune response to parasites and in the molecular cloning of dozens of genes encoding for potentially protective proteins, no definitive step has yet been made towards operational vaccines against major human parasitic diseases. The reasons for our prese...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1989.tb00551.x
更新日期：1989-12-01 00:00:00
abstract：:Aged animals and humans exhibit a decreased T-cell activation response although they also exhibit increased susceptibility to responses to self-antigens and a loss of self-tolerance. The age-related alteration in T-cell reactivity, polyclonal expansion of T cells, and enhanced production of autoantibodies may reflect ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2005.00270.x
更新日期：2005-06-01 00:00:00
abstract：:Viruses are obligatory intracellular parasites, whose replication depends on components encoded by the virus and pathways and functions of the host cell. In addition to the pathways required for viral synthesis, viruses activate multiple mechanisms to evade immune attack, promoting viral propagation while avoiding or ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2010.00909.x
更新日期：2010-05-01 00:00:00
abstract：:Complement is a humoral factor of innate immunity and plays important roles in immune surveillance and clearance of invading pathogens. Mammalian complement consists of the classical (antibody-dependent), the alternative (antibody-independent) and the lectin (triggered by mannose-binding lectin) pathways of activation...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01250.x
更新日期：1998-12-01 00:00:00
abstract：:Clarifying the signals that lead to dendritic cell (DC) development and identifying cellular intermediates on their way to DC differentiation are essential steps to understand the dynamic regulation of number, localization, and functionality of these cells. In the past decade, much knowledge on cytokines, transcriptio...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2009.00877.x
更新日期：2010-03-01 00:00:00
abstract：:Work in the SCID-hu system has progressed significantly over the past 3-4 years. Reliable SCID-hu constructs can now be created for the evaluation of long-term multilineage human hematopoiesis, human immune function, and HIV infection of human hematolymphoid organs in vivo. Given these constructs, a variety of therape...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1991.tb00615.x
更新日期：1991-12-01 00:00:00
abstract：:Natural killer cells employ a diverse arsenal of effector mechanisms to target intracellular pathogens. Differentiation of natural killer (NK) cell activation pathways occurs along a continuum from reliance on innate pro-inflammatory cytokines and stress-induced host ligands through to interaction with signals derived...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12798
更新日期：2020-01-01 00:00:00
abstract：:Unique Vγ2Vδ2 (Vγ9Vδ2) T cells existing only in human and non-human primates, account for the majority of circulating γδ T cells in human adults. Vγ2Vδ2 T cells are the sole γδ T-cell subpopulation capable of recognizing the microbial (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) produced by selected pathoge...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12927
更新日期：2020-11-01 00:00:00
abstract：:Bach2 is a basic region-leucine zipper (bZip) transcription factor that forms heterodimers with small Maf oncoproteins and binds to target genes, thus repressing their expression. Bach2 is required for class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes in activated B cells. Bach2 ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12201
更新日期：2014-09-01 00:00:00
abstract：:CD4(+) T lymphocytes orchestrate adaptive immune responses by differentiating into various subsets of effector T cells such as T-helper 1 (Th1), Th2, Th17, and regulatory T cells. These subsets have been generally described by master transcription factors that dictate the expression of cytokines and receptors, which u...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12055
更新日期：2013-05-01 00:00:00
abstract：:Inflammasome biology is one of the most exciting and rapidly growing areas in immunology. Over the past 10 years, inflammasomes have been recognized for their roles in the host defense against invading pathogens and in the development of cancer, auto-inflammatory, metabolic, and neurodegenerative diseases. Assembly of...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12296
更新日期：2015-05-01 00:00:00
abstract：:Natural killer (NK) cells of inbred mice reject allogeneic bone-marrow cells, and NK cells of F1 hybrid mice can reject parental bone-marrow cells (hybrid resistance). In some cases these patterns of rejection can be mimicked in vitro by utilizing IL-2 cultured NK effector cells and allogeneic or parental T-lymphoblas...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1997.tb00937.x
更新日期：1997-02-01 00:00:00
abstract：:NF-κB proteins were identified in the search for mechanisms that regulate B-lymphocyte-specific transcription of immunoglobulin κ light chain genes. Twenty-five years later, though the function of the κB site in the enhancer remains enigmatic, NF-κB proteins have been shown to have important roles in B-cell developmen...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2012.01106.x
更新日期：2012-03-01 00:00:00
abstract：:Cells of the monocyte/macrophage system originate from the bone marrow, reach the organs via the blood, immigrate through postcapillary venules and further differentiate into organ-specific tissue macrophages. In rats and other species, activated monocytes/macrophages aggravate autoimmune reactions, rejection of non-v...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2001.1840104.x
更新日期：2001-12-01 00:00:00
abstract：:In this review we address questions which must be considered if better attempts are to be made to treat all persons presently infected with human immunodeficiency virus (HIV). There are thirty million people in the world presently living with HIV, only 10% of whom are likely to be able to access currently available dr...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1999.tb01337.x
更新日期：1999-08-01 00:00:00
abstract：:Peptide/protein display libraries are powerful tools for identifying and manipulating receptor/ligand pairs. While the large size of bacterial phage display libraries has made them the platform of choice in many applications, often considerable engineering has been required to achieve display of properly folded and ac...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2006.00365.x
更新日期：2006-04-01 00:00:00
abstract：:The mammalian gastrointestinal (GI) tract is colonized by trillions of beneficial commensal bacteria that are essential for promoting normal intestinal physiology. While the majority of commensal bacteria are found in the intestinal lumen, many species have also adapted to colonize different anatomical locations in th...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12186
更新日期：2014-07-01 00:00:00
abstract：:The activation of the complement system by canonical and non-canonical mechanisms results in the generation of multiple C3 and C5 cleavage fragments including anaphylatoxins C3a and C5a as well as opsonizing C3b/iC3b. It is now well appreciated that anaphylatoxins not only act as pro-inflammatory mediators but as immu...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12473
更新日期：2016-11-01 00:00:00
abstract：:There is now convincing evidence that autoreactive CD8+ T cells can contribute to the pathogenesis of organ-specific autoimmune diseases. In the non-obese diabetic mouse, there is direct evidence that beta-islet cell-specific CD8+ cytotoxic T cells have a pathogenic effect. In human diseases such as autoimmune diabete...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1999.tb01308.x
更新日期：1999-06-01 00:00:00
abstract：:Basal, activation, and arrest signaling in T cells determines survival, coordinates responses to pathogens, and, when dysregulated, leads to loss of self-tolerance and autoimmunity. At the T-cell surface, transmembrane glycoproteins interact with galectins via their N-glycans, forming a molecular lattice that regulate...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2009.00796.x
更新日期：2009-07-01 00:00:00
abstract：:MHC class I molecules function to present peptides comprised of eight to 11 residues to CD8+ T lymphocytes. Here we review the efforts of our laboratory to understand how cells generate such peptides from viral gene products. We particularly focus on the nature of substrates acted on by cytosolic proteases, the contri...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1999.tb01359.x
更新日期：1999-12-01 00:00:00
abstract：:Malaria, caused by the infection with parasites of the germs Plasmodium, is one of the three most important infectious diseases worldwide, along with tuberculosis and infection with human immunodeficiency virus. Natural killer (NK) cells are lymphocytes classically involved in the early defense against viral infection...
journal_title：Immunological reviews
pub_type： 杂志文章
doi：10.1111/j.1600-065X.2006.00446.x
更新日期：2006-12-01 00:00:00
abstract：:Human T cell hybridomas were generated by several techniques and the supernatants generated were screened for activity on human B cells. Three general activities were noted; B cell proliferation factor ( BCPF ), B cell differentiation factor (BCDF), and an IgA isotype-specific helper factor. BCPF acts on B cells to in...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1984.tb00479.x
更新日期：1984-04-01 00:00:00
abstract：:The general thrust of this volume is to review the roles of accessory cells in regulating T and B lymphocytes. To that end, we have summarized the evidence that indicates the crucial role that Langerhans cells play in the induction and expression of immunity to antigens that gain access to, or arise within, skin. Lang...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1990.tb00572.x
更新日期：1990-10-01 00:00:00
abstract：:T cells are key players of the mammalian adaptive immune system. They experience different mechanical microenvironments during their life cycle, from the thymus, secondary lymph organs, and peripheral tissues that are free of externally applied force, but display variable substrate rigidities to the blood and lymphati...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12122
更新日期：2013-11-01 00:00:00
abstract：:In animals and in humans, T-cell therapy can cure advanced disseminated leukemia that would otherwise be fatal. The therapeutic effect of immune T cells is quantitative. As the dose of effector T cells is increased, survival is proportionately increased. Therefore, effective T-cell therapy is predicated on the ability...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1997.tb00982.x
更新日期：1997-06-01 00:00:00
abstract：:The initiation of T lymphocyte responses within secondary lymphoid organs involves interactions with different subsets of dendritic cells (DCs). Recent studies have revealed the complexity of microanatomical organization within lymphoid organs. Exactly how T cells and DCs locate each other and the type of cellular int...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12753
更新日期：2019-05-01 00:00:00
abstract：:The expression of L3T4 and Lyt-2 cell surface molecules separates T cells into two broad, non-overlapping subsets: typical T helper cells are L3T4+ Lyt-2- whereas most T killer cells and their precursors are L3T4- Lyt-2+. This review compares highly purified populations of unprimed L3T4+ and Lyt-2+ cells for their cap...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1986.tb01489.x
更新日期：1986-06-01 00:00:00
abstract：:The pattern of polymorphisms at MHC loci was studied by computer simulations and by DNA sequence analyses, with special reference to synonymous and non-synonymous divergence among alleles. A model of overdominance plus short-term selection was simulated for a gene family with allelic and non-allelic gene conversion. I...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1999.tb01401.x
更新日期：1999-02-01 00:00:00
