Cd4

Summary

Gene Symbol: Cd4
Description: CD4 antigen
Alias: L3T4, Ly-4, T-cell surface glycoprotein CD4, T-cell differentiation antigen L3T4, T-cell surface antigen T4/Leu-3
Species: mouse
Products:     Cd4

Top Publications

  1. Leung R, Thomson K, Gallimore A, Jones E, van Den Broek M, Sierro S, et al. Deletion of the CD4 silencer element supports a stochastic mechanism of thymocyte lineage commitment. Nat Immunol. 2001;2:1167-73 pubmed
    The mechanism of T cell lineage commitment remains controversial; to examine it we deleted the CD4-silencer element in the germ line of a mouse using a combination of gene targeting and Cre/LoxP-mediated recombination...
  2. Marie J, Liggitt D, Rudensky A. Cellular mechanisms of fatal early-onset autoimmunity in mice with the T cell-specific targeting of transforming growth factor-beta receptor. Immunity. 2006;25:441-54 pubmed
    ..Peripheral CD4+ and CD8+ T cells with TGF-beta-receptor II (TGF-betaRII) deficiency activated cytolytic and T helper 1 (Th1) ..
  3. Wildt K, Sun G, Grueter B, Fischer M, Zamisch M, Ehlers M, et al. The transcription factor Zbtb7b promotes CD4 expression by antagonizing Runx-mediated activation of the CD4 silencer. J Immunol. 2007;179:4405-14 pubmed
    The persistence of CD4 expression is a key event distinguishing the differentiation of MHC class II-restricted thymocytes into CD4 T cells from that of MHC class I-restricted thymocytes into CD8 T cells...
  4. Veiga Fernandes H, Coles M, Foster K, Patel A, Williams A, Natarajan D, et al. Tyrosine kinase receptor RET is a key regulator of Peyer's patch organogenesis. Nature. 2007;446:547-51 pubmed
    ..We further show that a CD45+CD4-CD3-Il7Ralpha-c-Kit+CD11c+ haematopoietic population expressing lymphotoxin has an important role in the formation ..
  5. Xiong W, Zhao Y, Prall A, Greiner T, Baxter B. Key roles of CD4+ T cells and IFN-gamma in the development of abdominal aortic aneurysms in a murine model. J Immunol. 2004;172:2607-12 pubmed
    ..However, the role of CD4(+) T cells, the most abundant infiltrates in aneurysmal aortic tissue, is uncertain...
  6. Wang L, Wildt K, Zhu J, Zhang X, Feigenbaum L, Tessarollo L, et al. Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4(+) T cells. Nat Immunol. 2008;9:1122-30 pubmed publisher
    The transcription factors GATA-3 and ThPOK are required for intrathymic differentiation of CD4(+) T cells, but their precise functions in this process remain unclear...
  7. Vondenhoff M, Desanti G, Cupedo T, Bertrand J, Cumano A, Kraal G, et al. Separation of splenic red and white pulp occurs before birth in a LTalphabeta-independent manner. J Leukoc Biol. 2008;84:152-61 pubmed publisher
    ..The postnatal development of the splenic white pulp, involving the influx of T cells, depends on LTalpha1beta2 expressed by B cells. ..
  8. Sato T, Ohno S, Hayashi T, Sato C, Kohu K, Satake M, et al. Dual functions of Runx proteins for reactivating CD8 and silencing CD4 at the commitment process into CD8 thymocytes. Immunity. 2005;22:317-28 pubmed
    To understand how CD8 expression is regulated during the transition process from CD4+8+ (CD4 and CD8 double positive, DP) to CD4-8+ (CD8 single positive, CD8SP) cells in the thymus, the involvement of Runx proteins in the alteration of ..
  9. Muroi S, Naoe Y, Miyamoto C, Akiyama K, Ikawa T, Masuda K, et al. Cascading suppression of transcriptional silencers by ThPOK seals helper T cell fate. Nat Immunol. 2008;9:1113-21 pubmed publisher
    b>CD4 and the transcription factor ThPOK are essential for the differentiation of major histocompatibility complex class II-restricted thymocytes into the helper T cell lineage; their genes (Cd4 and Zbtb7b (called 'ThPOK' here)) are ..

More Information

Publications63

  1. He X, Park K, Wang H, He X, Zhang Y, Hua X, et al. CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK transcription-factor locus. Immunity. 2008;28:346-58 pubmed publisher
    The transcription factor ThPOK is necessary and sufficient to trigger adoption of the CD4 lymphocyte fate. Here we investigate the regulation of ThPOK expression and its subsequent control of CD4+ T cell commitment...
  2. Yu M, Wan M, Zhang J, Wu J, Khatri R, Chi T. Nucleoprotein structure of the CD4 locus: implications for the mechanisms underlying CD4 regulation during T cell development. Proc Natl Acad Sci U S A. 2008;105:3873-8 pubmed publisher
    The CD4 gene is regulated in a stage-specific manner during T cell development, being repressed in CD4(-)CD8(-) double-negative (DN) and CD8 cells, but expressed in CD4(+)CD8(+) double-positive (DP) and CD4 cells...
  3. Chong M, Simpson N, Ciofani M, Chen G, Collins A, Littman D. Epigenetic propagation of CD4 expression is established by the Cd4 proximal enhancer in helper T cells. Genes Dev. 2010;24:659-69 pubmed publisher
    ..memory during lineage diversification, we employed targeted mutation of a positive-acting cis element in the Cd4 locus to determine the impact on CD4 expression and the differentiation of CD4(+) helper T cells in mice...
  4. Eberl G, Marmon S, Sunshine M, Rennert P, Choi Y, Littman D. An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells. Nat Immunol. 2004;5:64-73 pubmed
    ..This early LTi cell-mediated activation of lymph node and Peyer's patch mesenchyma forms the necessary platform for the subsequent development of mature lymphoid tissues. ..
  5. Yi J, Ingram J, Zajac A. IL-21 deficiency influences CD8 T cell quality and recall responses following an acute viral infection. J Immunol. 2010;185:4835-45 pubmed publisher
    b>CD4 T cells are principal producers of IL-21 and are often required for optimal CD8 T cell responses...
  6. Vondenhoff M, Greuter M, Goverse G, Elewaut D, Dewint P, Ware C, et al. LTbetaR signaling induces cytokine expression and up-regulates lymphangiogenic factors in lymph node anlagen. J Immunol. 2009;182:5439-45 pubmed publisher
    ..Furthermore, the same signals may regulate lymphangiogenesis to the lymph node through induction of VEGF-C. ..
  7. Fuller M, Khanolkar A, Tebo A, Zajac A. Maintenance, loss, and resurgence of T cell responses during acute, protracted, and chronic viral infections. J Immunol. 2004;172:4204-14 pubmed
    ..b>CD4-deficient mice cannot control infection with certain strains of LCMV, but do mount multi-epitope-specific CD8 T ..
  8. Sun Z, Unutmaz D, Zou Y, Sunshine M, Pierani A, Brenner Morton S, et al. Requirement for RORgamma in thymocyte survival and lymphoid organ development. Science. 2000;288:2369-73 pubmed
    ..RORgamma thus regulates the survival of CD4+8+ thymocytes and may control the temporal window during which thymocytes can undergo positive selection...
  9. Xu Y, Banerjee D, Huelsken J, Birchmeier W, Sen J. Deletion of beta-catenin impairs T cell development. Nat Immunol. 2003;4:1177-82 pubmed
    ..In addition, beta-catenin also seemed to be a target of TCR-CD3 signals in thymocytes and mature T cells. These data indicate that beta-catenin-mediated signals are required for normal T cell development. ..
  10. Chi T, Wan M, Zhao K, Taniuchi I, Chen L, Littman D, et al. Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes. Nature. 2002;418:195-9 pubmed
    Thymic development produces two sub-lineages of T cells expressing either CD4 or CD8 co-receptors that assist antibody production and mediate cell killing, respectively...
  11. Zou Y, Sunshine M, Taniuchi I, Hatam F, Killeen N, Littman D. Epigenetic silencing of CD4 in T cells committed to the cytotoxic lineage. Nat Genet. 2001;29:332-6 pubmed
    The process of thymocyte development culminates in the maturation of helper (CD4+) and cytotoxic (CD8+) T cells from their common precursors, the CD4+CD8+ double-positive cells...
  12. Fahlén L, Read S, Gorelik L, Hurst S, Coffman R, Flavell R, et al. T cells that cannot respond to TGF-beta escape control by CD4(+)CD25(+) regulatory T cells. J Exp Med. 2005;201:737-46 pubmed
    b>CD4(+)CD25(+) regulatory T (T reg) cells play a pivotal role in control of the immune response...
  13. Meier D, Bornmann C, Chappaz S, Schmutz S, Otten L, Ceredig R, et al. Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells. Immunity. 2007;26:643-54 pubmed
    Development of Peyer's patches and lymph nodes requires the interaction between CD4+ CD3- IL-7Ralpha+ lymphoid-tissue inducer (LTi) and VCAM-1+ organizer cells...
  14. Leitenberg D, Boutin Y, Constant S, Bottomly K. CD4 regulation of TCR signaling and T cell differentiation following stimulation with peptides of different affinities for the TCR. J Immunol. 1998;161:1194-203 pubmed
    To define the role of CD4 in modulating T cell signaling pathways and regulating Th1 and Th2 differentiation, we have examined the activation and differentiation characteristics of naive T cells from CD4 mutant mice...
  15. Sarafova S, Erman B, Yu Q, Van Laethem F, Guinter T, Sharrow S, et al. Modulation of coreceptor transcription during positive selection dictates lineage fate independently of TCR/coreceptor specificity. Immunity. 2005;23:75-87 pubmed
    ..More importantly, by placing CD4 protein expression under the control of CD8 transcriptional regulatory elements, we demonstrate that cessation of ..
  16. Malek T, Yu A, Vincek V, Scibelli P, Kong L. CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2. Immunity. 2002;17:167-78 pubmed
    ..Here, we show that CD4(+)CD25(+) regulatory T cells were not readily detected in IL-2Rbeta(-/-) mice, but the production of functional CD4(..
  17. Riberdy J, Mostaghel E, Doyle C. Disruption of the CD4-major histocompatibility complex class II interaction blocks the development of CD4(+) T cells in vivo. Proc Natl Acad Sci U S A. 1998;95:4493-8 pubmed
    The experiments presented in this report were designed to specifically examine the role of CD4-major histocompatibility complex (MHC) class II interactions during T cell development in vivo...
  18. Peffault De Latour R, Dujardin H, Mishellany F, Burlen Defranoux O, Zuber J, Marques R, et al. Ontogeny, function, and peripheral homeostasis of regulatory T cells in the absence of interleukin-7. Blood. 2006;108:2300-6 pubmed
    ..of disease was due to the fact that IL-7 is dispensable for the ontogeny, function, and homeostasis of regulatory CD4+ T cells...
  19. Wang Q, Malherbe L, Zhang D, Zingler K, Glaichenhaus N, Killeen N. CD4 promotes breadth in the TCR repertoire. J Immunol. 2001;167:4311-20 pubmed
    A diverse population of MHC class II-restricted CD4 lineage T cells develops in mice that lack expression of the CD4 molecule...
  20. Adoro S, Erman B, Sarafova S, Van Laethem F, Park J, Feigenbaum L, et al. Targeting CD4 coreceptor expression to postselection thymocytes reveals that CD4/CD8 lineage choice is neither error-prone nor stochastic. J Immunol. 2008;181:6975-83 pubmed
    The mechanism by which CD4/CD8 lineage choice is coordinated with TCR specificity during positive selection remains an unresolved problem in immunology...
  21. Mackerness K, Cox M, Lilly L, Weaver C, Harrington L, Zajac A. Pronounced virus-dependent activation drives exhaustion but sustains IFN-? transcript levels. J Immunol. 2010;185:3643-51 pubmed publisher
    ..Thus, posttranscription regulatory mechanisms likely disable this effector module. ..
  22. Shedlock D, Whitmire J, Tan J, MacDonald A, Ahmed R, Shen H. Role of CD4 T cell help and costimulation in CD8 T cell responses during Listeria monocytogenes infection. J Immunol. 2003;170:2053-63 pubmed
    b>CD4 T cells are known to assist the CD8 T cell response by activating APC via CD40-CD40 ligand (L) interactions...
  23. Lucas P, Kim S, Mackall C, Telford W, Chu Y, Hakim F, et al. Dysregulation of IL-15-mediated T-cell homeostasis in TGF-beta dominant-negative receptor transgenic mice. Blood. 2006;108:2789-95 pubmed
    T-cell subpopulations, defined by their expression of CD4, CD8, naive, and memory cell-surface markers, occupy distinct homeostatic compartments that are regulated primarily by cytokines...
  24. Park J, Adoro S, Lucas P, Sarafova S, Alag A, Doan L, et al. 'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR. Nat Immunol. 2007;8:1049-59 pubmed
    ..This dynamic interplay induces individual CD8+ T cells to express CD8 in quantities appropriate for the self-specificity of their TCR, promoting the engagement of self ligands, yet avoiding autoreactivity. ..
  25. Taniuchi I, Osato M, Egawa T, Sunshine M, Bae S, Komori T, et al. Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Cell. 2002;111:621-33 pubmed
    T lymphocytes differentiate in discrete stages within the thymus. Immature thymocytes lacking CD4 and CD8 coreceptors differentiate into double-positive cells (CD4(+)CD8(+)), which are selected to become either CD4(+)CD8(-)helper cells ..
  26. Adlam M, Siu G. Hierarchical interactions control CD4 gene expression during thymocyte development. Immunity. 2003;18:173-84 pubmed
    b>CD4 gene regulation provides an ideal model for understanding the molecular events that drive T cell development...
  27. Pena Rossi C, Zuckerman L, Strong J, Kwan J, Ferris W, Chan S, et al. Negative regulation of CD4 lineage development and responses by CD5. J Immunol. 1999;163:6494-501 pubmed
    ..Here we show that the development and responses of CD4 lineage T cells are regulated by the function of CD5. Thymocytes expressing the I-Ad-restricted DO11...
  28. Taniuchi I, Sunshine M, Festenstein R, Littman D. Evidence for distinct CD4 silencer functions at different stages of thymocyte differentiation. Mol Cell. 2002;10:1083-96 pubmed
    An intronic silencer within the CD4 gene is the critical cis regulatory element for T cell subset-specific expression of CD4...
  29. Tyznik A, Sun J, Bevan M. The CD8 population in CD4-deficient mice is heavily contaminated with MHC class II-restricted T cells. J Exp Med. 2004;199:559-65 pubmed
    In experiments to study the impact of deficiency in CD4+ T cell help on the magnitude of CD8+ cytotoxic T cell response to pathogens, it was noted that in CD4 gene knockout mice, the CD8 population made significant responses to several ..
  30. Wang Q, Strong J, Killeen N. Homeostatic competition among T cells revealed by conditional inactivation of the mouse Cd4 gene. J Exp Med. 2001;194:1721-30 pubmed
    Absence of CD4 impairs the efficiency of T cell receptor (TCR) signaling in response to major histocompatibility complex (MHC) class II-presented peptides...
  31. Leithäuser F, Meinhardt Krajina T, Fink K, Wotschke B, Moller P, Reimann J. Foxp3-expressing CD103+ regulatory T cells accumulate in dendritic cell aggregates of the colonic mucosa in murine transfer colitis. Am J Pathol. 2006;168:1898-909 pubmed
    ..Therefore, we analyzed the putative function of large intestinal dendritic cell (DC) aggregates, to which donor CD4+ T cells selectively home before colitis becomes manifest...
  32. Grayson M, Cheung D, Rohlfing M, Kitchens R, Spiegel D, Tucker J, et al. Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia. J Exp Med. 2007;204:2759-69 pubmed
    ..FceRIa(-/-) mice had decreased CCL28 and recruitment of IL-13-producing CD4(+) T cells to the lung after viral infection...
  33. Ishikawa H, Hisaeda H, Taniguchi M, Nakayama T, Sakai T, Maekawa Y, et al. CD4(+) v(alpha)14 NKT cells play a crucial role in an early stage of protective immunity against infection with Leishmania major. Int Immunol. 2000;12:1267-74 pubmed
    ..In those resistant mice, CD4(+) NKT cells prominently increased in their regional lymph node and were the main effector cells at least for an ..
  34. Joffre O, Santolaria T, Calise D, Al Saati T, Hudrisier D, Romagnoli P, et al. Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes. Nat Med. 2008;14:88-92 pubmed
    ..Here we show that in mice treated with clinically acceptable levels of irradiation, regulatory CD4+CD25+Foxp3+ T cells stimulated in vitro with alloantigens induced long-term tolerance to bone marrow and subsequent ..
  35. Sarafova S, Van Laethem F, Adoro S, Guinter T, Sharrow S, Feigenbaum L, et al. Upregulation of CD4 expression during MHC class II-specific positive selection is essential for error-free lineage choice. Immunity. 2009;31:480-90 pubmed publisher
    ..cessation of T cell receptor (TCR) signaling during positive selection, with persistent TCR signaling required for CD4 lineage choice...
  36. Mendiratta S, Martin W, Hong S, Boesteanu A, Joyce S, van Kaer L. CD1d1 mutant mice are deficient in natural T cells that promptly produce IL-4. Immunity. 1997;6:469-77 pubmed
    ..NT cells promptly produce large amounts of IL-4, suggesting that these cells can influence the differentiation of CD4+ effector T cell subsets. We have generated mice that carry a mutant CD1d1 gene...
  37. Siu G, Wurster A, Duncan D, Soliman T, Hedrick S. A transcriptional silencer controls the developmental expression of the CD4 gene. EMBO J. 1994;13:3570-9 pubmed
    The appropriate expression of the CD4 glycoprotein is required for T-cell function and development...
  38. Heemskerk M, Schilham M, Schoemaker H, Spierenburg G, Spaan W, Boog C. Activation of virus-specific major histocompatibility complex class II-restricted CD8+ cytotoxic T cells in CD4-deficient mice. Eur J Immunol. 1995;25:1109-12 pubmed
    ..hepatitis in mice and rats and induces a response of major histocompatibility complex (MHC) class II-restricted CD4+ cytotoxic T cells, protecting mice against acute infection...
  39. Killeen N, Littman D. Helper T-cell development in the absence of CD4-p56lck association. Nature. 1993;364:729-32 pubmed
    The CD4 and CD8 glycoproteins are expressed on helper and cytoxic T lymphocytes, respectively, and have important functions in the differentiation and activation of these cells...
  40. Rahemtulla A, Fung Leung W, Schilham M, Kundig T, Sambhara S, Narendran A, et al. Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4. Nature. 1991;353:180-4 pubmed
    ..They also express two key surface coreceptors, CD4 and CD8, which are involved in the interaction with their ligands...
  41. Matechak E, Killeen N, Hedrick S, Fowlkes B. MHC class II-specific T cells can develop in the CD8 lineage when CD4 is absent. Immunity. 1996;4:337-47 pubmed
    The generation of mature CD4 T cells from CD4+CD8+ precursor thymocytes usually requires corecognition of class II MHC by a TCR and CD4, while the production of mature CD8 T cells requires corecognition of class I MHC by a TCR and CD8...
  42. Davis C, Killeen N, Crooks M, Raulet D, Littman D. Evidence for a stochastic mechanism in the differentiation of mature subsets of T lymphocytes. Cell. 1993;73:237-47 pubmed
    Thymocytes that coexpress the CD4 and CD8 glycoproteins differentiate into mature CD4+ helper or CD8+ cytotoxic cells depending on whether their antigen receptors are specific for MHC class II or class I molecules, respectively...
  43. Sawada S, Scarborough J, Killeen N, Littman D. A lineage-specific transcriptional silencer regulates CD4 gene expression during T lymphocyte development. Cell. 1994;77:917-29 pubmed
    During development of T lymphocytes, differential regulation of expression of the CD4 and CD8 glycoproteins is coupled to the choice of one of two pathways of differentiation...
  44. Veillette A, Bookman M, Horak E, Bolen J. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell. 1988;55:301-8 pubmed
    The CD4 and CD8 T cell antigens are thought to transduce an independent signal during the process of T cell activation...
  45. Littman D, Gettner S. Unusual intron in the immunoglobulin domain of the newly isolated murine CD4 (L3T4) gene. Nature. 1987;325:453-5 pubmed
    ..for a variety of functional studies, we have isolated, sequenced and expressed cDNA clones encoding the murine CD4 (L3T4) glycoprotein...
  46. Wineman J, Gilmore G, Gritzmacher C, Torbett B, Muller Sieburg C. CD4 is expressed on murine pluripotent hematopoietic stem cells. Blood. 1992;80:1717-24 pubmed
    We show here for the first time that pluripotent hematopoietic stem cells express the CD4 antigen...
  47. Law Y, Yeung R, Mamalaki C, Kioussis D, Mak T, Flavell R. Human CD4 restores normal T cell development and function in mice deficient in murine CD4. J Exp Med. 1994;179:1233-42 pubmed
    The ability of a human coreceptor to function in mice was investigated by generating human CD4 (hCD4)-expressing transgenic mice on a mouse CD4-deficient (mCD4-/-) background...
  48. Locksley R, Reiner S, Hatam F, Littman D, Killeen N. Helper T cells without CD4: control of leishmaniasis in CD4-deficient mice. Science. 1993;261:1448-51 pubmed
    Expression of either the CD4 or CD8 glycoproteins discriminates two functionally distinct lineages of T lymphocytes...
  49. Rahemtulla A, Kundig T, Narendran A, Bachmann M, Julius M, Paige C, et al. Class II major histocompatibility complex-restricted T cell function in CD4-deficient mice. Eur J Immunol. 1994;24:2213-8 pubmed
    Previously, we and others have demonstrated that CD4-deficient mice have a normal number of T cells and B cells with a significant population of CD4-8-TcR alpha beta+ T cells...
  50. Killeen N, Sawada S, Littman D. Regulated expression of human CD4 rescues helper T cell development in mice lacking expression of endogenous CD4. EMBO J. 1993;12:1547-53 pubmed
    During T cell development, precursor thymocytes that co-express the CD4 and CD8 glycoproteins give rise to mature progeny expressing one of these molecules to the exclusion of the other...
  51. Miceli M, Parnes J. Role of CD4 and CD8 in T cell activation and differentiation. Adv Immunol. 1993;53:59-122 pubmed
  52. Veillette A, Bookman M, Horak E, Samelson L, Bolen J. Signal transduction through the CD4 receptor involves the activation of the internal membrane tyrosine-protein kinase p56lck. Nature. 1989;338:257-9 pubmed
    The CD4 T-cell surface antigen is an integral membrane glycoprotein of relative molecular mass 55,000 which binds class II major histocompatibility complex (MHC) molecules expressed on antigen presenting cells (APCs)...
  53. von Herrath M, Yokoyama M, Dockter J, Oldstone M, Whitton J. CD4-deficient mice have reduced levels of memory cytotoxic T lymphocytes after immunization and show diminished resistance to subsequent virus challenge. J Virol. 1996;70:1072-9 pubmed
    Although primary antiviral CD8+ cytotoxic T lymphocytes (CTL) can be induced in mice depleted of CD4+ T cells, the role of CD4+ T lymphocytes in the generation and maintenance of antiviral memory CTL is uncertain...
  54. Seong R, Chamberlain J, Parnes J. Signal for T-cell differentiation to a CD4 cell lineage is delivered by CD4 transmembrane region and/or cytoplasmic tail. Nature. 1992;356:718-20 pubmed
    Mature T cells express either CD4 or CD8 on their surface...