Gene Symbol: Cd4
Description: Cd4 molecule
Alias: W3/25, p55, T-cell surface glycoprotein CD4, CD4 antigen, T-cell surface antigen T4/Leu-3, W3/25 antigen
Species: rat
Products:     Cd4

Top Publications

  1. 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...
  2. van den Broek M, Van de Langerijt L, van Bruggen M, Billingham M, van den Berg W. Treatment of rats with monoclonal anti-CD4 induces long-term resistance to streptococcal cell wall-induced arthritis. Eur J Immunol. 1992;22:57-61 pubmed
    To investigate the role of CD4+ cells in the induction and maintenance of streptococcal cell wall (SCW)-induced arthritis, Lewis rats were treated with a monoclonal antibody against rat CD4 (W3/25)...
  3. Nakatsuji T. Better-surviving liver grafts by the injection of anti-CD2 antibody: the important roles of host CD8+ and CD2+CD28+ T cells in chronic graft rejection and beta type platelet-derived growth factor receptor (PDGFR-beta) expression on apoptotic liver gr. Tohoku J Exp Med. 1999;187:215-25 pubmed
    ..rats with both splenectomy and anti-CD2 MAb injection, pulmonary apoptosis was induced with the 6-16% reductions of CD4+ lymphocytes. Prolonged graft survival was observed in only one of the 9 rats...
  4. 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...
  5. Luo K, Sefton B. Cross-linking of T-cell surface molecules CD4 and CD8 stimulates phosphorylation of the lck tyrosine protein kinase at the autophosphorylation site. Mol Cell Biol. 1990;10:5305-13 pubmed
    ..p56lck, a lymphocyte-specific tyrosine protein kinase, binds to the cytoplasmic tails of the T-cell surface molecules CD4 and CD8...
  6. Ye Q, Wang L, Wells A, Tao R, Han R, Davidson A, et al. BAFF binding to T cell-expressed BAFF-R costimulates T cell proliferation and alloresponses. Eur J Immunol. 2004;34:2750-9 pubmed
    ..We report that the binding of BAFF to BAFF-R expressed by a subset of primarily CD4(+) T cells costimulates T cell activation and allo-proliferation in vitro and in vivo, and that mice with a ..
  7. Kisielow J, Kopf M, Karjalainen K. SCART scavenger receptors identify a novel subset of adult gammadelta T cells. J Immunol. 2008;181:1710-6 pubmed
    ..Characterization of SCART2 positive immature and peripheral gammadelta T cells suggests that they undergo lineage specification in the thymus and belong to a new IL-17-producing subset with distinct homing capabilities. ..
  8. Jefferies W, Green J, Williams A. Authentic T helper CD4 (W3/25) antigen on rat peritoneal macrophages. J Exp Med. 1985;162:117-27 pubmed
    ..New monoclonal antibodies against the rat CD4 antigen, MRC OX-35 through OX-38, are described, all of which label peritoneal macrophages from normal and athymic rats...
  9. Murata K, Iwata T, Nakashima S, Fox Talbot K, Qian Z, Wilkes D, et al. C4d deposition and cellular infiltrates as markers of acute rejection in rat models of orthotopic lung transplantation. Transplantation. 2008;86:123-9 pubmed publisher
    ..Furthermore, the histological features of our allografts support the concept that posttransplant capillaritis is a form of humoral rejection. ..

More Information


  1. Beyers A, Spruyt L, Williams A. Molecular associations between the T-lymphocyte antigen receptor complex and the surface antigens CD2, CD4, or CD8 and CD5. Proc Natl Acad Sci U S A. 1992;89:2945-9 pubmed
    ..for molecular complexes, and associations were demonstrated between the TCR complex and the surface antigens CD2, CD4, or CD8 and CD5 in normal rat T cells...
  2. Kennedy M, Glaccum M, Brown S, Butz E, Viney J, Embers M, et al. Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med. 2000;191:771-80 pubmed
    ..Moreover, the ability to rescue lymphoid defects in IL-15(-/-) mice by IL-15 administration represents a powerful means by which to further elucidate the biological roles of this cytokine. ..
  3. Nataf S, Garcion E, Darcy F, Chabannes D, Muller J, Brachet P. 1,25 Dihydroxyvitamin D3 exerts regional effects in the central nervous system during experimental allergic encephalomyelitis. J Neuropathol Exp Neurol. 1996;55:904-14 pubmed
    ..This effect was accompanied by a profound inhibition of CD4 antigen expression by central nervous system (CNS) infiltrating monocytes/macrophages and parenchymal microglia...
  4. Rabanal M, Franch A, Noe V, Pelegri C, Ciudad C, Castellote C, et al. CD4 expression decrease by antisense oligonucleotides: inhibition of rat T CD4+ cell reactivity. Oligonucleotides. 2003;13:217-28 pubmed
    In previous studies, we have demonstrated the inhibition of CD4 expression in rat lymphocytes treated with phorbol myristate acetate (PMA) by antisense oligonucleotides (AS-ODNs) directed against the AUG start region of the cd4 gene...
  5. Aiken C, Konner J, Landau N, Lenburg M, Trono D. Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain. Cell. 1994;76:853-64 pubmed
    b>CD4 is crucial for antigen-driven helper T cell signaling and is used as receptor by the human immunodeficiency virus (HIV)...
  6. Nissler K, Pohlers D, Huckel M, Simon J, Brauer R, Kinne R. Anti-CD4 monoclonal antibody treatment in acute and early chronic antigen induced arthritis: influence on macrophage activation. Ann Rheum Dis. 2004;63:1470-7 pubmed
    To investigate the indirect effects of anti-CD4 treatment on the functions of macrophages (CD4(-) in mice) in the acute and early chronic phase of mouse antigen induced arthritis (AIA)...
  7. Ludovico Martins H, Silva C, Teodoro W, Martini Filho D, Noronha I. Analysis of different staining techniques for c4d detection in renal allograft biopsies. Transplant Proc. 2009;41:862-5 pubmed publisher
    ..In conclusion, these results demonstrated that frozen-IHC and paraffin-IF can be considered alternative techniques to frozen-IF for C4d detection. The paraffin-IHC technique displayed the lowest concordance rate for C4d detection. ..
  8. Yagi R, Junttila I, Wei G, Urban J, Zhao K, Paul W, et al. The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma. Immunity. 2010;32:507-17 pubmed publisher
    The transcription factor GATA3 is crucial for the differentiation of naive CD4(+) T cells into T helper 2 (Th2) cells...
  9. Hu M, Deshpande A, Schlichting N, Hinds E, Mao C, Dose M, et al. CDK6 kinase activity is required for thymocyte development. Blood. 2011;117:6120-31 pubmed publisher
    ..This role of CDK6 as a downstream mediator of Notch identifies CDK6 kinase activity as a potential therapeutic target in human lymphoid malignancies. ..
  10. Cheng A, Rowley B, Pao W, Hayday A, Bolen J, Pawson T. Syk tyrosine kinase required for mouse viability and B-cell development. Nature. 1995;378:303-6 pubmed
  11. Suzuki M, Hirao A, Mizuno A. Microtubule-associated [corrected] protein 7 increases the membrane expression of transient receptor potential vanilloid 4 (TRPV4). J Biol Chem. 2003;278:51448-53 pubmed
    ..The activated current was abolished by actin-freezing but not by microtubule-freezing reagents. We therefore believe that MAP7 may enhance the membrane expression of TRPV4 and possibly link cytoskeletal microfilaments. ..
  12. Hosoya T, Kuroha T, Moriguchi T, Cummings D, Maillard I, Lim K, et al. GATA-3 is required for early T lineage progenitor development. J Exp Med. 2009;206:2987-3000 pubmed publisher
    ..Thus, GATA-3 is required for the cell-autonomous development of the earliest characterized thymic T cell progenitors. ..
  13. Sakai T, Agui T, Muramatsu Y, Yamada T, Hisaeda H, Himeno K, et al. Function of CD4 molecules in LEC rat thymocytes. J Vet Med Sci. 1996;58:1125-7 pubmed
    Long-Evans Cinnamon (LEC) rats show a novel maturational arrest from CD4+8+ to CD4+8- thymocytes but a cause of this mutation is not identified...
  14. 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...
  15. Garcia Martinez L, Appleby M, Staehling Hampton K, Andrews D, Chen Y, McEuen M, et al. A novel mutation in CD83 results in the development of a unique population of CD4+ T cells. J Immunol. 2004;173:2995-3001 pubmed
    Using a mouse mutagenesis screen, we have identified CD83 as being critical for the development of CD4(+) T cells and for their function postactivation...
  16. Kedainis R, Koch M, Brennan D, Liapis H. Focal C4d+ in renal allografts is associated with the presence of donor-specific antibodies and decreased allograft survival. Am J Transplant. 2009;9:812-9 pubmed publisher
    ..There was a clear trend toward worse graft survival in patients with focal C4d+ in this time interval, but focal C4d+ compared to both diffuse C4d+ and C4d-groups was not statistically significant (p = 0.08). ..
  17. Bry L, Brenner M. Critical role of T cell-dependent serum antibody, but not the gut-associated lymphoid tissue, for surviving acute mucosal infection with Citrobacter rodentium, an attaching and effacing pathogen. J Immunol. 2004;172:433-41 pubmed
    ..In contrast, CD4-/- or TCR-beta-/- mice develop polymicrobial sepsis and end-organ damage, and succumb during acute infection, ..
  18. Matsuzaki J, Tsuji T, Chamoto K, Takeshima T, Sendo F, Nishimura T. Successful elimination of memory-type CD8+ T cell subsets by the administration of anti-Gr-1 monoclonal antibody in vivo. Cell Immunol. 2003;224:98-105 pubmed
    ..Thus, we initially demonstrated that anti-Gr-1 mAb might become a good tool to investigate a precise role for memory-type CD8(+) T cells in vivo. ..
  19. Wang J, Meijers R, Xiong Y, Liu J, Sakihama T, Zhang R, et al. Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule. Proc Natl Acad Sci U S A. 2001;98:10799-804 pubmed
    The structural basis of the interaction between the CD4 coreceptor and a class II major histocompatibility complex (MHC) is described...
  20. Huse M, Eck M, Harrison S. A Zn2+ ion links the cytoplasmic tail of CD4 and the N-terminal region of Lck. J Biol Chem. 1998;273:18729-33 pubmed
    ..Lck is a lymphoid-specific, Src family protein-tyrosine kinase that is known to interact with the T-cell coreceptors, CD4 and CD8...
  21. Liao F, Alkhatib G, Peden K, Sharma G, Berger E, Farber J. STRL33, A novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1. J Exp Med. 1997;185:2015-23 pubmed
    The chemokine receptors CXCR4, CCR2B, CCR3, and CCR5 have recently been shown to serve along with CD4 as coreceptors for HIV-1...
  22. Zheng Y, Sundstrom S, Lyttle C, Teuscher C. Differential expression of estrogen-regulated CD4 and Ia positive cells in the immature rat uterus. J Leukoc Biol. 1989;46:493-6 pubmed
    ..only Sprague-Dawley rats exhibit an estrogen regulated increase in the number of cells expressing immunoreactive CD4 and Ia, suggesting that the differential responsiveness to the effects of estradiol between the two strains of rats ..
  23. Chu K, Niu X, Williams L. A Fas-associated protein factor, FAF1, potentiates Fas-mediated apoptosis. Proc Natl Acad Sci U S A. 1995;92:11894-8 pubmed
    ..Therefore, FAF1 is an unusual protein that binds to the wild type but not the inactive point mutant of Fas. FAF1 potentiates Fas-induced cell killing and is a candidate signal transducing molecule in the regulation of apoptosis. ..
  24. Mandal M, Borowski C, Palomero T, Ferrando A, Oberdoerffer P, Meng F, et al. The BCL2A1 gene as a pre-T cell receptor-induced regulator of thymocyte survival. J Exp Med. 2005;201:603-14 pubmed
    ..Finally, we suggest that pre-TCR-induced A1 overexpression can contribute to T cell leukemia in both mice and humans. ..
  25. Wang L, Carr T, Xiong Y, Wildt K, Zhu J, Feigenbaum L, et al. The sequential activity of Gata3 and Thpok is required for the differentiation of CD1d-restricted CD4+ NKT cells. Eur J Immunol. 2010;40:2385-90 pubmed publisher
    While most CD4(+) T cells are MHC class II-restricted, a small subset, including the CD1d-restricted 'invariant' NKT (iNKT) cells, are selected on non-classical MHC-I or MHC-I-like molecules...
  26. Tomer Y, Blank M, Shoenfeld Y. Suppression of experimental antiphospholipid syndrome and systemic lupus erythematosus in mice by anti-CD4 monoclonal antibodies. Arthritis Rheum. 1994;37:1236-44 pubmed
    To investigate whether anti-CD4 antibodies can suppress experimental antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) induced by an anti-DNA monoclonal antibody (MAb)...
  27. Davis S, Ward H, Puklavec M, Willis A, Williams A, Barclay A. High level expression in Chinese hamster ovary cells of soluble forms of CD4 T lymphocyte glycoprotein including glycosylation variants. J Biol Chem. 1990;265:10410-8 pubmed
    The CD4 cell surface antigen is of interest as a marker of T lymphocytes that recognize foreign antigens in the context of MHC Class II antigen, as a receptor for the human immunodeficiency virus (HIV) and as a member of the ..
  28. Doyle C, Strominger J. Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature. 1987;330:256-9 pubmed
    The CD4 glycoprotein is expressed on T-helper and cytotoxic lymphocytes which are restricted to class II major histocompatibility complex (MHC) antigens on target cells...
  29. Balamuth F, Brogdon J, Bottomly K. CD4 raft association and signaling regulate molecular clustering at the immunological synapse site. J Immunol. 2004;172:5887-92 pubmed
    ..This study demonstrates a novel function for the CD4 coreceptor in regulating molecular clustering at the immunological synapse site...
  30. Turner M, Mee P, Costello P, Williams O, Price A, Duddy L, et al. Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature. 1995;378:298-302 pubmed
    ..Finally, we show that Syk is not required for signalling through the IL-2 and G-CSF receptors. ..
  31. Miceli M, Parnes J. Role of CD4 and CD8 in T cell activation and differentiation. Adv Immunol. 1993;53:59-122 pubmed
  32. Almolda B, Costa M, Montoya M, Gonzalez B, Castellano B. CD4 microglial expression correlates with spontaneous clinical improvement in the acute Lewis rat EAE model. J Neuroimmunol. 2009;209:65-80 pubmed publisher
    b>CD4 is a molecule commonly expressed on the surface of T-helper lymphocytes with a recognized critical role in the antigen presentation process that has also been reported in monocytes and macrophages, although its role in these cells ..
  33. Sedgwick J, Mason D. The mechanism of inhibition of experimental allergic encephalomyelitis in the rat by monoclonal antibody against CD4. J Neuroimmunol. 1986;13:217-32 pubmed
    ..experimental allergic encephalomyelitis (EAE) were treated with a monoclonal antibody (MAb) which binds to the CD4 antigen of rat helper/inducer T cells...
  34. Shiow L, Roadcap D, Paris K, Watson S, Grigorova I, Lebet T, et al. The actin regulator coronin 1A is mutant in a thymic egress-deficient mouse strain and in a patient with severe combined immunodeficiency. Nat Immunol. 2008;9:1307-15 pubmed publisher
  35. Wiest D, Ashe J, Howcroft T, Lee H, Kemper D, Negishi I, et al. A spontaneously arising mutation in the DLAARN motif of murine ZAP-70 abrogates kinase activity and arrests thymocyte development. Immunity. 1997;6:663-71 pubmed
    Development of immature CD4+ CD8+ thymocytes into functionally mature CD4+ and CD8+ T cells is driven by selection events that require signals transduced through the T cell antigen receptor (TCR)...
  36. 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...
  37. Zhen A, Krutzik S, Levin B, Kasparian S, Zack J, Kitchen S. CD4 ligation on human blood monocytes triggers macrophage differentiation and enhances HIV infection. J Virol. 2014;88:9934-46 pubmed publisher
    A unique aspect of human monocytes, compared to monocytes from many other species, is that they express the CD4 molecule. However, the role of the CD4 molecule in human monocyte development and function is not known...
  38. Brady R, Dodson E, Dodson G, Lange G, Davis S, Williams A, et al. Crystal structure of domains 3 and 4 of rat CD4: relation to the NH2-terminal domains. Science. 1993;260:979-83 pubmed
    The CD4 antigen is a membrane glycoprotein of T lymphocytes that interacts with major histocompatibility complex class II antigens and is also a receptor for the human immunodeficiency virus...
  39. Chong A, Ma L, Yin D, Shen J, Blinder L, XiuLong X, et al. Non-depleting anti-CD4, but not anti-CD8, antibody induces long-term survival of xenogeneic and allogeneic hearts in alpha1,3-galactosyltransferase knockout (GT-Ko) mice. Xenotransplantation. 2000;7:275-83 pubmed
    ..In this study, we compared the ability of non-depleting anti-CD4 and anti-CD8 to control rejection and antibody production in GT-Ko mice following xenograft and allograft ..
  40. Ayliffe W, Alam Y, Bell E, McLeod D, Hutchinson I. Prolongation of rat corneal graft survival by treatment with anti-CD4 monoclonal antibody. Br J Ophthalmol. 1992;76:602-6 pubmed
    ..Though CD4+ cells were not eliminated completely by anti-CD4 monoclonal antibodies there was a profound delay in the rejection ..
  41. Clark S, Jefferies W, Barclay A, Gagnon J, Williams A. Peptide and nucleotide sequences of rat CD4 (W3/25) antigen: evidence for derivation from a structure with four immunoglobulin-related domains. Proc Natl Acad Sci U S A. 1987;84:1649-53 pubmed
    ..Subsequently, the human OKT4 antigen (now called CD4) was described, and cell distribution and functional data suggested that W3/25 and OKT4 antigens were homologous...
  42. Sant Angelo D, Waterbury G, Preston Hurlburt P, Yoon S, Medzhitov R, Hong S, et al. The specificity and orientation of a TCR to its peptide-MHC class II ligands. Immunity. 1996;4:367-76 pubmed
    ..Based on these results, we propose an orientation for the TCR of this cloned line and argue for its generality. ..
  43. Moldovan M, Yachou A, Levesque K, Wu H, Hendrickson W, Cohen E, et al. CD4 dimers constitute the functional component required for T cell activation. J Immunol. 2002;169:6261-8 pubmed
    The CD4 molecule plays a key role in the development and activation of helper T cells. Dimerization and oligomerization is often a necessary step in the function of several cell surface receptors...
  44. Gartlan K, Belz G, Tarrant J, Minigo G, Katsara M, Sheng K, et al. A complementary role for the tetraspanins CD37 and Tssc6 in cellular immunity. J Immunol. 2010;185:3158-66 pubmed publisher
    ..Therefore, in the absence of both CD37 and Tssc6, immune function is further altered when compared with CD37(-/-) or Tssc6(-/-) mice, demonstrating a complementary role for these two molecules in cellular immunity...
  45. Nabozny G, Cobbold S, Waldmann H, Kong Y. Suppression in murine experimental autoimmune thyroiditis: in vivo inhibition of CD4+ T cell-mediated resistance by a nondepleting rat CD4 monoclonal antibody. Cell Immunol. 1991;138:185-96 pubmed
    ..To study Ts action in vivo, we used a rat IgG2a monoclonal antibody (mAb), YTS 177.9, which modulates CD4 antigen in vivo without depleting CD4+ cells...
  46. Simpson S, Mizoguchi E, Allen D, Bhan A, Terhorst C. Evidence that CD4+, but not CD8+ T cells are responsible for murine interleukin-2-deficient colitis. Eur J Immunol. 1995;25:2618-25 pubmed
    ..Although this disease is marked by substantial infiltration of the colon by CD8+ and CD4+ T lymphocytes, no function has yet been assigned to these T cell subsets in the development of colitis in the IL-..
  47. Negishi I, Motoyama N, Nakayama K, Senju S, Hatakeyama S, Zhang Q, et al. Essential role for ZAP-70 in both positive and negative selection of thymocytes. Nature. 1995;376:435-8 pubmed
    ..Here we show that mice lacking ZAP-70 had neither CD4 nor CD8 single-positive T cells, but human ZAP-70 reconstituted both CD4 and CD8 single-positive populations...
  48. Pohlers D, Schmidt Weber C, Franch A, Kuhlmann J, Bräuer R, Emmrich F, et al. Differential clinical efficacy of anti-CD4 monoclonal antibodies in rat adjuvant arthritis is paralleled by differential influence on NF-kappaB binding activity and TNF-alpha secretion of T cells. Arthritis Res. 2002;4:184-9 pubmed
    The aim of this study was to analyze the differential effects of three anti-CD4 monoclonal antibodies (mAbs) (with distinct epitope specifities) in the treatment of rat adjuvant arthritis (AA) and on T-cell function and signal ..
  49. Bouvier G, Watrin F, Naspetti M, Verthuy C, Naquet P, Ferrier P. Deletion of the mouse T-cell receptor beta gene enhancer blocks alphabeta T-cell development. Proc Natl Acad Sci U S A. 1996;93:7877-81 pubmed
    ..deletion, whether a selectable marker gene is present or not, show a block in alphabeta T-cell development at the CD4-CD8- double-negative cell stage, whereas the number of gammadelta+ T cells is normal, few CD4+CD8+ double-positive ..
  50. Du C, Liu C, Kang J, Zhao G, Ye Z, Huang S, et al. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol. 2009;10:1252-9 pubmed publisher
    ..Our data show a critical role for microRNA in T(H)-17 differentiation and the pathogenesis of multiple sclerosis. ..
  51. Hazenbos W, Gessner J, Hofhuis F, Kuipers H, Meyer D, Heijnen I, et al. Impaired IgG-dependent anaphylaxis and Arthus reaction in Fc gamma RIII (CD16) deficient mice. Immunity. 1996;5:181-8 pubmed
    ..These results indicate a prominent role for Fc gamma RIII in inflammatory and anaphylactic responses, making this receptor a potential target in immunotherapy...
  52. Wu H, Kwong P, Hendrickson W. Dimeric association and segmental variability in the structure of human CD4. Nature. 1997;387:527-30 pubmed
    b>CD4 is a co-receptor in the cellular immune response...
  53. Kirchgessner H, Dietrich J, Scherer J, Isomaki P, Korinek V, Hilgert I, et al. The transmembrane adaptor protein TRIM regulates T cell receptor (TCR) expression and TCR-mediated signaling via an association with the TCR zeta chain. J Exp Med. 2001;193:1269-84 pubmed