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Gene Review

CD4  -  CD4 molecule

Homo sapiens

Synonyms: T-cell surface antigen T4/Leu-3, T-cell surface glycoprotein CD4
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Disease relevance of CD4

  • Of considerable interest is the recent discovery that some chemokines function as HIV-suppressive factors by interacting with chemokine receptors which, together with CD4, were recognized as the binding sites for HIV-1 [1].
  • The finding that one chemokine receptor can function as a primary viral receptor strongly suggests that the HIV envelope glycoprotein contains a binding site for these proteins and that differences in the affinity and/or the availability of this site can extend the host range of these viruses to include a number of CD4-negative cell types [2].
  • CD4-independent infection by HIV-2 is mediated by fusin/CXCR4 [2].
  • This animal model provides a powerful in vivo tool to dissect the human CD4-human class II MHC interaction, especially its role in human autoimmune diseases, superantigen-mediated diseases, and acquired immunodeficiency syndrome (AIDS) [3].
  • This therapeutic regimen resulted in a remarkable increase in the number of CD4+ cells and in the prolonged reduction of the levels of viremia [4].

Psychiatry related information on CD4


High impact information on CD4

  • We have modeled HIV-1 neutralization by a CD4 binding site monoclonal Ab, and we propose that neutralization takes place by inhibition of the interaction between gp120 and the target cell membrane receptors as a result of steric hindrance [10].
  • Similar data implicate protein tyrosine kinases in signaling from the CD4 and CD8 coreceptors and the beta chain of the IL-2 receptor [11].
  • By secreting interleukins, CD4 alpha/beta TH1 cells activate MP, converting them from a habitat to a potent effector cell; TH2-dependent activities seem to be of minor importance [12].
  • The three main components are the hypervariable alpha: beta heterodimer that confers specificity and its attendant invariant chains CD3 gamma, delta, and epsilon and the zeta:zeta or zeta:eta, the CD4 or CD8 coreceptor, and CD45 [13].
  • The T cell receptor as a multicomponent signalling machine: CD4/CD8 coreceptors and CD45 in T cell activation [13].

Chemical compound and disease context of CD4


Biological context of CD4


Anatomical context of CD4


Associations of CD4 with chemical compounds

  • Thus, it appears that CD8 alpha may depend more on a protein kinase C-mediated signaling pathway, whereas CD4 may rely on greater tyrosine kinase activation [21].
  • In addition to CD4, different gp120 isolates bind to the alpha- or beta-chemokine receptors CXCR4 and CCR5, respectively [26].
  • Inhibition of CD4 cross-linking-induced lymphocytes apoptosis by vesnarinone as a novel immunomodulating agent: vesnarinone inhibits Fas expression and apoptosis by blocking cytokine secretion [27].
  • A population with homing potential for lymph nodes (L selectin(+) CCR7(+)) exists only within a small subset of CD4 NKT cells [28].
  • Environmental antigens (Ag) were used to evaluate IP-10's effect on CD4-dependent, chloroquine-sensitive cytokine synthesis [29].
  • Using blocking reagents neutralizing CD4 binding, experimental systems where MHC class II molecules are absent and recombinant alpha-GalCer/CD1d complexes, we show that CD4 potentiates human iNKT cell activation by engaging CD1d molecules [30].
  • Such control of infection correlated with stronger responses to CD4i epitopes in the rhFLSC-vaccinated animals, compared with macaques immunized with gp120, cross-linked gp120-CD4 complexes, or soluble CD4 alone [31].
  • Overall, the present study found a strong correlation between CD4 C868T and increased susceptibility to HIV-1 infection [32].

Physical interactions of CD4


Enzymatic interactions of CD4

  • This association may allow CD45 to engage and dephosphorylate lck or another CD4- or CD8-associated substrate in order to reset the receptor complex to receive a new set of stimuli [36].
  • Legionella pneumophila protease inactivates interleukin-2 and cleaves CD4 on human T cells [37].

Regulatory relationships of CD4


Other interactions of CD4

  • Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones [20].
  • T cell-derived LCF may contribute to recruitment of eosinophils and CD4+ mononuclear cells concomitantly at inflammatory reactions [24].
  • When transfected into nonhuman NIH 3T3 cells expressing human CD4, the STRL33 cDNA rendered these cells competent to fuse with cells expressing HIV-1 envelope glycoproteins (Envs) [44].
  • In contrast the activation-independent adhesion of CD4+ T cell to ELAM-1 molecules does not lead to T cell stimulation as measured by proliferation, IL-2R alpha expression, or cytokine release [45].
  • We have developed a genetic system, called degrakine, that specifically and stably inactivates chemokine receptors (CKR) by redirecting the ability of the HIV-1 protein, Vpu, to degrade CD4 in the endoplasmic reticulum (ER) via the host proteasome machinery [46].

Analytical, diagnostic and therapeutic context of CD4

  • Using an optical biosensor, we found that CD4-induced (CD4i) epitopes recognized by mAbs 17b and 48d were more exposed on 8x than on IIIB gp120 [47].
  • In this study, the cytokine profile of cord and adult blood lymphocytes and lymphocyte subsets has been assessed at the single-cell level by flow cytometry, using CD4/CD8 and CD45RA/CD45RO markers [48].
  • Based on a three-color immunofluorescence analysis, the mean relative fluorescence intensity of HLA-DR was smaller on CD34+/CD4+ cells in comparison with CD34+/ CD4- cells [49].
  • The kinetics of association between CD4 or CD8 and CD45 was measured by fluorescence resonance energy transfer and confirmed by immunoprecipitation of dithiobis succinimidylpropionate or disuccinimidyl suberate cross-linked 125I-labeled resting or activated T cells [36].
  • After 8 to 42 days in organ culture, both Leu-3+ (CD4) and Leu-2+ (CD8) subsets were found in each culture, in a ratio that varied from 0.2 to 5.0, which was not significantly different than the results of in situ immunoperoxidase staining of the uncultured biopsy [50].


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  15. A functional, discontinuous HIV-1 gp120 C3/C4 domain-derived, branched, synthetic peptide that binds to CD4 and inhibits MIP-1alpha chemokine binding. Howie, S.E., Fernandes, M.L., Heslop, I., Hewson, T.J., Cotton, G.J., Moore, M.J., Innes, D., Ramage, R., Harrison, D.J. FASEB J. (1999) [Pubmed]
  16. CD4-independent use of Rhesus CCR5 by human immunodeficiency virus Type 2 implicates an electrostatic interaction between the CCR5 N terminus and the gp120 C4 domain. Lin, G., Lee, B., Haggarty, B.S., Doms, R.W., Hoxie, J.A. J. Virol. (2001) [Pubmed]
  17. CD4-independent infection of astrocytes by human immunodeficiency virus type 1: requirement for the human mannose receptor. Liu, Y., Liu, H., Kim, B.O., Gattone, V.H., Li, J., Nath, A., Blum, J., He, J.J. J. Virol. (2004) [Pubmed]
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  21. Evidence for differential intracellular signaling via CD4 and CD8 molecules. Ravichandran, K.S., Burakoff, S.J. J. Exp. Med. (1994) [Pubmed]
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  23. Crystal structure of an HIV-binding recombinant fragment of human CD4. Ryu, S.E., Kwong, P.D., Truneh, A., Porter, T.G., Arthos, J., Rosenberg, M., Dai, X.P., Xuong, N.H., Axel, R., Sweet, R.W. Nature (1990) [Pubmed]
  24. CD4-mediated stimulation of human eosinophils: lymphocyte chemoattractant factor and other CD4-binding ligands elicit eosinophil migration. Rand, T.H., Cruikshank, W.W., Center, D.M., Weller, P.F. J. Exp. Med. (1991) [Pubmed]
  25. Dendritic cells freshly isolated from human blood express CD4 and mature into typical immunostimulatory dendritic cells after culture in monocyte-conditioned medium. O'Doherty, U., Steinman, R.M., Peng, M., Cameron, P.U., Gezelter, S., Kopeloff, I., Swiggard, W.J., Pope, M., Bhardwaj, N. J. Exp. Med. (1993) [Pubmed]
  26. Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Kaul, M., Lipton, S.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  27. Inhibition of CD4 cross-linking-induced lymphocytes apoptosis by vesnarinone as a novel immunomodulating agent: vesnarinone inhibits Fas expression and apoptosis by blocking cytokine secretion. Oyaizu, N., McCloskey, T.W., Than, S., Pahwa, S. Blood (1996) [Pubmed]
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  29. Human IP-10 selectively promotes dominance of polyclonally activated and environmental antigen-driven IFN-gamma over IL-4 responses. Gangur, V., Simons, F.E., Hayglass, K.T. FASEB J. (1998) [Pubmed]
  30. CD4 engagement by CD1d potentiates activation of CD4+ invariant NKT cells. Thedrez, A., de Lalla, C., Allain, S., Zaccagnino, L., Sidobre, S., Garavaglia, C., Borsellino, G., Dellabona, P., Bonneville, M., Scotet, E., Casorati, G. Blood (2007) [Pubmed]
  31. Antibodies to CD4-induced sites in HIV gp120 correlate with the control of SHIV challenge in macaques vaccinated with subunit immunogens. DeVico, A., Fouts, T., Lewis, G.K., Gallo, R.C., Godfrey, K., Charurat, M., Harris, I., Galmin, L., Pal, R. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  32. A common CD4 gene variant is associated with an increased risk of HIV-1 infection in Kenyan female commercial sex workers. Oyugi, J.O., Vouriot, F.C., Alimonti, J., Wayne, S., Luo, M., Land, A.M., Ao, Z., Yao, X., Sekaly, R.P., Elliott, L.J., Simonsen, J.N., Ball, T.B., Jaoko, W., Kimani, J., Plummer, F.A., Fowke, K.R. J. Infect. Dis. (2009) [Pubmed]
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