Abstract:
:It is clear by now that cell-to-cell interactions involving a variety of signals are required for effective immune response. The data reviewed here suggest that CD40-CD40L interactions are critical for development of CD4 T-cell-dependent effector functions. Lack of this important interaction results in greatly reduced activation of CD4 T cells, while successful interaction of these molecules results in full activation of these T cells. Consequently, the absence of CD40-CD40L interactions leads to impairment of T-cell effector such as help for B-cell differentiation and class switch, activation of monocytes and macrophages to produce cytokines and to kill intracellular pathogens, and activation of autoreactive T cells to mount an autoimmune response. The effector functions of T cells controlled by CD40-CD40L interactions in a successful immune response are given in Table I. Data presented so far suggest that CD40-CD40L interactions play a role in early signalling events, where interactions of this kind are required to induce expression of costimulatory molecules on APC. One possible sequence of events in that APC, like DC, take up antigens at the site of injury or infection and migrate to lymph nodes, where they present antigens complexed with MHC class II molecules to naive T cells. This results in expression of CD40L on T cells. Coupling of this newly expressed CD40L on T cells with CD40 on APC results in expression of the costimulatory activity of the APC. At this time the costimulatory signal provided by the APC is received by the T cells via CD28/CTLA-4, which drives the cell to enter into cell cycle and complete T cell activation. T cells thereby activated can now enter into secondary cognate CD40-CD40L-dependent effector recognition with B cells to switch Ig class, macrophages to produce cytokines and new DC carrying the same antigen to up-regulate costimulatory activity. A tight regulation of expression of CD40L on T cells and costimulatory activity on APC would prevent activation of unwanted bystander T cells. The coupling of activation of the APC primed with the cognate antigen to the activation of the T-cell specific for that antigen in this model provides an additional regulatory step in the initiation of the immune response. This also suggests that a limited number of T cells/APC will be activated, both of which will be specific in nature. This additional step may be important for safeguarding against an autoimmune response. In addition, the fact that CD40L uniquely seems to play this role suggests that selective immunotherapies to treat autoimmune disease and prevent graft rejection can be targeted on this molecule. On the other hand, CD40-directed approaches to up-regulate costimulatory activity on APC could be developed to fight tumor growth, contain infections and treat immunodeficiencies.
journal_name
Immunol Revjournal_title
Immunological reviewsauthors
Grewal IS,Flavell RAdoi
10.1111/j.1600-065x.1996.tb00921.xsubject
Has Abstractpub_date
1996-10-01 00:00:00pages
85-106eissn
0105-2896issn
1600-065Xjournal_volume
153pub_type
杂志文章,评审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 a...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.0105-2896.2006.00348.x
更新日期:2006-02-01 00:00:00
abstract::Immune responses to gastrointestinal nematodes have been studied extensively for over 80 years and intensively investigated over the last 30-40 years. The use of laboratory models has led to the discovery of new mechanisms of protective immunity and made major contributions to our fundamental understanding of both inn...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/imr.12188
更新日期:2014-07-01 00:00:00
abstract::The major histocompatibility complex (MHC) plays a central role in controlling immune responsiveness, susceptibility to certain diseases and histo-incompatibility. A physical map of the complete rat MHC, the RTI complex, is presented based on a PAC clonal contig (RT1n haplotype). Expression profiling of various tissue...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1034/j.1600-065x.2001.1840108.x
更新日期:2001-12-01 00:00:00
abstract::IgG dimers occurring in therapeutic Ig preparations have been characterized as Id-anti-Id, in that the sites of interaction are localized to the distal tips of the Fab arms. The observation that such dimers are prevalent in Ig or Igi.v. prepared from large plasma pools, but absent in preparations from a single individ...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065x.1994.tb00861.x
更新日期:1994-06-01 00:00:00
abstract::The AIDS pandemic is a global emergency and a preventive vaccine is urgently needed. CD4 and CD8 T-cell responses appear important in controlling human immunodeficiency virus (HIV)-1 in humans and simian immunodeficiency virus (SIV) in macaques. The utility of vaccines that induce high levels of SIV- or HIV-specific T...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1034/j.1600-065x.2001.1830108.x
更新日期:2001-10-01 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::Nuclear-factor κB (NF-κB) transcription factors are activated by a wide variety of stimuli in diverse cell types and control key aspects of immune function and development. Receptor-mediated activation of NF-κB appears to occur through two distinct signaling pathways termed as the canonical and non-canonical NF-κB pat...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2011.01059.x
更新日期:2011-11-01 00:00:00
abstract::Activation of immune cells to mediate an immune response is often triggered by potential 'danger' or 'stress' stimuli that the organism receives. Within the mitogen-activated protein kinases (MAPKs) family, the stress-activated protein kinase (SAPK) group was defined as group of kinases that activated by stimuli that ...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2008.00744.x
更新日期:2009-03-01 00:00:00
abstract::As biomedical research becomes increasingly data-intensive, it is increasingly essential to integrate genomic-scale datasets, so as to generate a more holistic picture of complex biological processes. The systems biology paradigm may differ in strategy from traditional reductionist scientific methods, but the goal rem...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2010.00998.x
更新日期:2011-03-01 00:00:00
abstract::The screening of tumor-derived expression libraries for antigens detected by high-titer immunoglobulin G antibodies from the sera of patients with cancer by SEREX (serological identification of antigens by recombinant expression cloning) allows a systematic search for antigens of human cancers. SEREX has led to the id...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1034/j.1600-065x.2002.18805.x
更新日期:2002-10-01 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::Reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS), including nitric oxide, are produced in cells by a variety of enzymatic and non-enzymatic mechanisms. At high levels, both types of oxidants are used to kill ingested organisms within phagocytes. At low levels, RNOS may diffuse outside cells whe...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2007.00513.x
更新日期:2007-06-01 00:00:00
abstract::Systems biology is the comprehensive and quantitative analysis of the interactions between all of the components of biological systems over time. Systems biology involves an iterative cycle, in which emerging biological problems drive the development of new technologies and computational tools. These technologies and ...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2008.00721.x
更新日期:2009-01-01 00:00:00
abstract::Because of its intrinsic virulence, Toxoplasma gondii induces a potent interleukin-12 (IL-12)-dependent cell-mediated immune response that shuts down the growth of the replicative tachyzoite stage, thus promoting host survival and successful transmission through predation. At the same time, this response must be tight...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.0105-2896.2004.00179.x
更新日期:2004-10-01 00:00:00
abstract::The interferon-gamma (IFN-gamma)/interleukin-12 (IL-12) pathway is a pivotal player in the immune system and is central to controlling mycobacterial infections. We highlight the most recent and relevant advances in understanding this pathway and their repercussions on basic and clinical science. Human mutations in IFN...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.0105-2896.2005.00227.x
更新日期:2005-02-01 00:00:00
abstract::Newfound relatives of the classical Fc receptors (FcR) have been provisionally named the Fc receptor homologs (FcRH). The recent identification of eight human and six mouse FcRH genes substantially increases the size and functional potential of the FcR family. The extended family of FcR and FcRH genes spans approximat...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1034/j.1600-065x.2002.19009.x
更新日期:2002-12-01 00:00:00
abstract::Studies of the regulation of gene expression historically focused on transcription. However, during stress and apoptosis, profound gene expression changes occur more rapidly and globally than is possible by regulating transcription. Posttranscriptional changes in mRNA processing and translation in response to diverse ...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/imr.12052
更新日期:2013-05-01 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::Studies in the last 20 years have given us a remarkable insight into the functional and phenotypic diversity of macrophages which reflects their integral role in host defence, homeostasis and pathogenesis. Mouse genetics, transcriptomic and epigenetic studies have provided an ontogenic and molecular perspective to the...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/imr.12603
更新日期:2017-11-01 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
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 mammalian Dok protein family has seven members (Dok-1-Dok-7). The Dok proteins share structural similarities characterized by the NH2-terminal pleckstrin homology and phosphotyrosine-binding domains followed by SH2 target motifs in the COOH-terminal moiety, indicating an adapter function. Indeed, Dok-1 was origina...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2009.00844.x
更新日期:2009-11-01 00:00:00
abstract::Five of the 10 human Toll-like receptors (TLRs) (TLR3, TLR4, TLR7, TLR8, and TLR9), and four of the 12 mouse TLRs (TLR3, TLR4, TLR7, TLR9) can trigger interferon (IFN)-alpha, IFN-beta, and IFN-lambda, which are critical for antiviral immunity. Moreover, TLR3, TLR7, TLR8, and TLR9 differ from TLR4 in two particularly i...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2007.00564.x
更新日期:2007-12-01 00:00:00
abstract::Mice infected with Listeria monocytogenes (LM) generate protective CD8 cells of varying specificity. One subset, unlike conventional LM-immune CD8 cells, can respond to antigen-presenting cells (APC) treated with heat-killed LM (HKLM). These cells proved to have surprisingly uniform specificity, recognizing a product ...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065x.1997.tb00998.x
更新日期:1997-08-01 00:00:00
abstract::Major histocompatibility complex class II (MHCII) molecules drive the development, activation and homeostasis of CD4* T-helper cells. They play a central role in key processes of the adaptive immune system, such as the generation of T-cell-mediated immune responses, the regulation of antibody production and the develo...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1034/j.1600-065x.2000.17813.x
更新日期:2000-12-01 00:00:00
abstract::Adoptive transfer of TCR-transgenic T cells uniformly expressing an identifiable TCR of known peptide/MHC specificity can be used to monitor the in vivo behavior of antigen-specific T cells. We have used this system to show that naive T cells are initially activated within the T-cell zones of secondary lymphoid tissue...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065x.1997.tb00959.x
更新日期:1997-04-01 00:00:00
abstract::The genes that encode molecules involved in antigen presentation within the class I and class II regions of the mammalian major histocompatibility complex (MHC) include several that are highly polymorphic. There is evidence that this polymorphism is maintained by positive selection, most likely overdominant selection,...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065x.1999.tb01381.x
更新日期:1999-02-01 00:00:00
abstract::Ozone (O(3)) and endotoxin are common environmental contaminants that cause asthma exacerbation. These pollutants have similar phenotype response characteristics, including induction of neutrophilic inflammation, changes in airway macrophage immunophenotypes, and ability to enhance response to inhaled allergen. Evoked...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2011.01035.x
更新日期:2011-07-01 00:00:00
abstract::During the past several years, we have been studying the circulating TCR gamma delta cells expressed in peripheral lymphoid tissues. Biochemical and molecular characterization of the TCR gamma delta heterodimers present on these TCR gamma delta cells identified 3 TCR gamma proteins, V gamma 2-C gamma 1, V gamma 1.2-C ...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065x.1991.tb00585.x
更新日期:1991-04-01 00:00:00
abstract::In the quest for effective immunization against complex diseases such as cancer, parasitic diseases, AIDS, and other viral infections, numerous peptides and recombinant proteins have been synthesized, examined for the ability to induce antibodies and CTLs, and tested for binding capability and therapeutic or prophylac...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065x.1995.tb00075.x
更新日期:1995-06-01 00:00:00