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 focus of intense study since then. This review deals with three formerly discrete topics that are gradually becoming interconnected: the role of TCR signaling in lineage commitment, the regulation of expression of the CD4 and CD8 genes, and transcriptional regulation of lineage commitment. It is widely accepted that TCR signaling exerts a decisive influence on lineage choice, although the underlying mechanism remains intensely debated. Current evidence suggests that both duration and intensity of TCR signaling may control lineage choice, as proposed by the kinetic signaling and quantitative instructive models, respectively. Alternate expression of the CD4 and CD8 genes is the most visible manifestation of lineage choice, and much progress has been made in defining the responsible cis elements and transcription factors. Finally, important clues to the molecular basis of lineage commitment have been provided by the recent identification of the transcription factor ThPOK as a key regulator of lineage choice. ThPOK is selectively expressed in class II-restricted cells at the CD4(+)8(lo) stage and is necessary and sufficient for development to the CD4 lineage. Given the central role of ThPOK in lineage commitment, understanding its upstream regulation and downstream gene targets is expected to reveal further important aspects of the molecular machinery underlying lineage commitment.
journal_name
Annu Rev Immunoljournal_title
Annual review of immunologyauthors
He X,Park K,Kappes DJdoi
10.1146/annurev.immunol.25.022106.141715subject
Has Abstractpub_date
2010-01-01 00:00:00pages
295-320eissn
0732-0582issn
1545-3278journal_volume
28pub_type
杂志文章,评审abstract::Although several laboratories have shown that the appearance of naturally occurring suppressor cells in the spleens of neonatal or irradiated mice is temporarily related to the ease of induction of tolerance, the characteristics of these cells and their regulatory functions have been poorly understood until recently. ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.02.040184.001251
更新日期:1984-01-01 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::Mast cells have existed long before the development of adaptive immunity, although they have been given different names. Thus, in the marine urochordate Styela plicata, they have been designated as test cells. However, based on their morphological characteristics (including prominent cytoplasmic granules) and mediator...
journal_title:Annual review of immunology
pub_type: 杂志文章
doi:10.1146/annurev-immunol-071719-094903
更新日期:2020-04-26 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
abstract::Over the past decade, key protein interactions contributing to T cell antigen recognition have been characterized in molecular detail. These have included interactions involving the T cell antigen receptor (TCR) itself, its coreceptors CD4 and CD8, the accessory molecule CD2, and the costimulatory receptors CD28 and C...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.21.120601.141036
更新日期:2003-01-01 00:00:00
abstract::NF-kappa B is a ubiquitous transcription factor. Nevertheless, its properties seem to be most extensively exploited in cells of the immune system. Among these properties are NF-kappa B's rapid posttranslational activation in response to many pathogenic signals, its direct participation in cytoplasmic/nuclear signaling...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.12.040194.001041
更新日期:1994-01-01 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::Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflamma...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-032713-120252
更新日期:2015-01-01 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::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::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::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::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::Dendritic cells (DCs) are professional antigen-presenting cells that have the ability to sense infection and tissue stress, sample and present antigen to T lymphocytes, and induce different forms of immunity and tolerance. The functional versatility of DCs depends on their remarkable ability to translate collectively ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.25.022106.141718
更新日期:2007-01-01 00:00:00
abstract::During the last decade the immunoglobulin J chain has indeed come of age. The amino-acid sequence has been determined for the mouse and human polypeptides, and the data obtained have established the uniqueness of the primary structure and its high degree of conservation in vertebrates. The biosynthesis of J chain has ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.03.040185.002233
更新日期:1985-01-01 00:00:00
abstract::The IL-10 family of cytokines consists of nine members: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, and the more distantly related IL-28A, IL-28B, and IL-29. Evolutionarily, IL-10 family cytokines emerged before the adaptive immune response. These cytokines elicit diverse host defense mechanisms, especially from epithel...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev-immunol-031210-101312
更新日期:2011-01-01 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::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::The transmembrane receptor Notch participates in diverse cell fate decisions throughout embryonic development. Notch receptors and their ligands are expressed in the mammalian thymus, raising the possibility that Notch could regulate T cell fate decisions. Expression of a constitutively activated form of Notch in deve...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.17.1.283
更新日期:1999-01-01 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::T cell development involves stepwise progression through defined stages that give rise to multiple T cell subtypes, and this is accompanied by the establishment of stage-specific gene expression. Changes in chromatin accessibility and chromatin modifications accompany changes in gene expression during T cell developme...
journal_title:Annual review of immunology
pub_type: 杂志文章
doi:10.1146/annurev-immunol-092719-082622
更新日期:2020-04-26 00:00:00
abstract::To combat infection, the fruit fly Drosophila melanogaster relies on multiple innate defense reactions, many of which are shared with higher organisms. These reactions include the use of physical barriers together with local and systemic immune responses. First, epithelia, such as those beneath the cuticle, in the ali...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.25.022106.141615
更新日期:2007-01-01 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::The discovery that genes in the major histocompatibility complex (MHC) play an important role in the immune response depended on the chance interaction of several unrelated events. The first, and most important, was the decision by Michael Sela to synthesize a series of branched, multichain, synthetic polypeptides bas...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.18.1.1
更新日期:2000-01-01 00:00:00
abstract::A family consisting of at least ten distinct novel 8-10 kd cytokines has been identified over the past 12 years. These cytokines exhibit from 20 to 45% homology in amino acid sequence, are probably all basic heparin-binding polypeptides, and have proinflammatory and reparative activities. The cDNA for these cytokines ...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.iy.09.040191.003153
更新日期:1991-01-01 00:00:00
abstract::This review examines the role of cross-presentation in tolerance and immunity. We discuss (a) the antigenic requirements for cross-presentation, (b) the phenotype of the antigen presenting cell (APC), (c) the cellular interactions and molecular signals involved in cross-priming, and (d) the factors that direct the imm...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.19.1.47
更新日期:2001-01-01 00:00:00
abstract::The mammalian Rel/NF-kappaB family of transcription factors, including RelA, c-Rel, RelB, NF-kappaB1 (p50 and its precursor p105), and NF-kappaB2 (p52 and its precursor p100), plays a central role in the immune system by regulating several processes ranging from the development and survival of lymphocytes and lymphoid...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.021908.132641
更新日期:2009-01-01 00:00:00
abstract::The transcription factor NF-kappa B, more than a decade after its discovery, remains an exciting and active area of study. The involvement of NF-kappa B in the expression of numerous cytokines and adhesion molecules has supported its role as an evolutionarily conserved coordinating element in the organism's response t...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.16.1.225
更新日期:1998-01-01 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::During the last several years, the mechanism of IFN gamma-dependent signal transduction has been the focus of intense investigation. This research has recently culminated in the elucidation of a comprehensive molecular understanding of the events that underlie IFN gamma-induced cellular responses. The structure and fu...
journal_title:Annual review of immunology
pub_type: 杂志文章,评审
doi:10.1146/annurev.immunol.15.1.563
更新日期:1997-01-01 00:00:00