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Gene Review

CD4  -  CD4 molecule

Canis lupus familiaris

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Disease relevance of CD4

  • Indole derivative 1 interferes with the interaction of the HIV surface protein gp120 with the host cell receptor CD4 [1].
  • The distribution of canine distemper virus (CDV) antigens was examined immunohistochemically with monoclonal antibodies specific for canine Thy-1, immunoglobulin (Ig) M, CD4, CD8, CD21 and CD45RB, and anti-measles virus nucleocapsid protein serum [2].
  • This was followed by a clinical remission, although a multifocal subacute synovitis was noted with inflammatory infiltrates of mononuclear cells (macrophages > CD8 > CD4) [3].
  • BMS-378806 is a prototype of novel HIV attachment inhibitors that block the gp120 and CD4 interaction, the first step of HIV-1 entry into cells [4].

High impact information on CD4

  • Dog leukocyte antigen nonidentical unrelated canine marrow grafts: enhancement of engraftment by CD4 and CD8 T cells [5].
  • CD4/CD45RA positive cells seem to be an important subpopulation of these CD45RA positive T-cells [6].
  • Whale CD4 cDNA contains 2662 base pairs and translates into a protein containing 455 amino acids [7].
  • Evolutionarily, the whale CD4 sequence is most similar to pig and structurally similar to dog and cat, in that all lack the cysteine pair in the V2 domain [7].
  • Molecular characterization of CD4 in an aquatic mammal provides information on the CD4 molecule itself and may provide insight into adaptive evolutionary changes of the immune system [7].

Biological context of CD4

  • Therapy with either the CD4 or the CD8 mAb, using no other immunosuppression, did not prolong graft survival [8].
  • Dietary lutein increased (P<0.05) lymphocyte proliferative response to all three mitogens and increased the percentages of cells expressing CD5, CD4, CD8 and major histocompatibility complex class II (MHC II) molecules [9].
  • Investigating the phenotype of lymphocytes from three different locations of the right lung, the cranial lobe lymphocytes show a lower CD4/CD8 ratio in comparison with PBL (1.81 +/- 0.35 vs. 1.12 +/- 0.31, n = 5; P < 0.02) [10].
  • Using immunochemistry on cytologic and histologic samples, the pleomorphic histiocytic cells were positive for CD1c, CD11ad, CD45, lysozyme, and vimentin, and were negative for CD3, CD4, CD79a, CD90, and pancytokeratin [11].

Anatomical context of CD4

  • The expression of CD4 by canine neutrophils is without precedent in other mammalian species; the functional significance of neutrophil CD4 expression is puzzling in light of the current understanding of the functions of CD4 which include it's role as a receptor for nonpolymorphic regions of MHC class II molecules [12].
  • However, in thymus the antibodies defined populations of double-positive, double-negative and single-positive cells that showed a progressive maturation consistent with that described for CD4 and CD8 in other mammalian species [12].
  • The CD4 to CD8 lymphocyte subset ratio (CD4:CD8) in peripheral blood was tested in 3 affected dogs and was within the normal range [13].
  • This report describes the immunocytochemical detection and distribution of different canine leucocytes antigens (Thy-1, CD5, CD4, CD8, MHC-II and B-cell antigen) by means of monoclonal antibodies (mAbs) in frozen tissue sections of lymphoid organs of the dog [14].
  • Focal cartilage erosion was due to adherent granulation tissue (CD4 > CD8 > macrophages) [3].

Associations of CD4 with chemical compounds

  • After PCR amplification two overlapping cDNA clones encoding the dog homologue of the human CD4 glycoprotein were identified [15].
  • Neither CD4 nor CD8 monoclonal antibodies given alone prolonged allografts survival (creatinine > or = 300 micromol/l) beyond 7 days [16].

Other interactions of CD4


Analytical, diagnostic and therapeutic context of CD4

  • Alone Thy-1 had little effect but, when combined with CD4, the median allograft survival time was increased to 15.5 days [17].
  • Reduction of the number of circulating T lymphocytes appears complementary to blockade of CD4 for immunosuppression, while blockade of CD4 combined with removal of CD8 also favours allograft survival [17].
  • Molecular cloning and characterization of CD4 in an aquatic mammal, the white whale Delphinapterus leucas [7].
  • Flow cytometry was also used to assess cell surface antigenic determinants (CD3, CD4, CD8, CD14, CD21, CD45RA, surface immunoglobulin) on peripheral blood mononuclear cells [18].
  • A directed search for antibiotics active in a syncytium formation inhibition assay using a co-culture of HeLa-T4 cells expressing CD4 antigen and BSC-1 cells expressing gp-120 led to the isolation of pradimicin S, a new member of the pradimicin family [19].


  1. Discovery of 4-benzoyl-1-[(4-methoxy-1H- pyrrolo[2,3-b]pyridin-3-yl)oxoacetyl]-2- (R)-methylpiperazine (BMS-378806): a novel HIV-1 attachment inhibitor that interferes with CD4-gp120 interactions. Wang, T., Zhang, Z., Wallace, O.B., Deshpande, M., Fang, H., Yang, Z., Zadjura, L.M., Tweedie, D.L., Huang, S., Zhao, F., Ranadive, S., Robinson, B.S., Gong, Y.F., Ricarrdi, K., Spicer, T.P., Deminie, C., Rose, R., Wang, H.G., Blair, W.S., Shi, P.Y., Lin, P.F., Colonno, R.J., Meanwell, N.A. J. Med. Chem. (2003) [Pubmed]
  2. Immunohistochemical analysis of the lymphoid organs of dogs naturally infected with canine distemper virus. Iwatsuki, K., Okita, M., Ochikubo, F., Gemma, T., Shin, Y.S., Miyashita, N., Mikami, T., Kai, C. J. Comp. Pathol. (1995) [Pubmed]
  3. Pathologic study of an experimental canine arthritis induced with Complete Freund's Adjuvant. Haak, T., Delverdier, M., Amardeilh, M.F., Oswald, I.P., Toutain, P.L. Clinical and experimental rheumatology. (1996) [Pubmed]
  4. Preclinical pharmacokinetics of a novel HIV-1 attachment inhibitor BMS-378806 and prediction of its human pharmacokinetics. Yang, Z., Zadjura, L., D'Arienzo, C., Marino, A., Santone, K., Klunk, L., Greene, D., Lin, P.F., Colonno, R., Wang, T., Meanwell, N., Hansel, S. Biopharmaceutics & drug disposition. (2005) [Pubmed]
  5. Dog leukocyte antigen nonidentical unrelated canine marrow grafts: enhancement of engraftment by CD4 and CD8 T cells. Panse, J.P., Bastianelli, C., Santos, E.B., Schwarzinger, I., Raff, R.F., Storb, R., Sandmaier, B.M. Transplantation (2003) [Pubmed]
  6. Lymphocyte subsets and CD45RA positive T-cells in normal canine cerebrospinal fluid. Tipold, A., Moore, P., Jungi, T.W., Sager, H., Vandevelde, M. J. Neuroimmunol. (1998) [Pubmed]
  7. Molecular cloning and characterization of CD4 in an aquatic mammal, the white whale Delphinapterus leucas. Romano, T.A., Ridgway, S.H., Felten, D.L., Quaranta, V. Immunogenetics (1999) [Pubmed]
  8. Immunosuppression of canine renal allograft recipients by CD4 and CD8 monoclonal antibodies. Watson, C.J., Cobbold, S.P., Davies, H.S., Rebello, P.R., Thiru, S., McNair, R., Rasmussen, A., Waldmann, H., Calne, R.Y., Metcalfe, S.M. Tissue Antigens (1994) [Pubmed]
  9. Dietary lutein stimulates immune response in the canine. Kim, H.W., Chew, B.P., Wong, T.S., Park, J.S., Weng, B.B., Byrne, K.M., Hayek, M.G., Reinhart, G.A. Vet. Immunol. Immunopathol. (2000) [Pubmed]
  10. Immunophenotyping of canine bronchoalveolar and peripheral blood lymphocytes. Dirscherl, P., Beisker, W., Kremmer, E., Mihalkov, A., Voss, C., Ziesenis, A. Vet. Immunol. Immunopathol. (1995) [Pubmed]
  11. Cerebrospinal fluid from a 10-year-old dog with a single seizure episode. Zimmerman, K., Almy, F., Carter, L., Higgins, M., Rossmeisl, J., Inzana, K., Duncan, R. Veterinary clinical pathology / American Society for Veterinary Clinical Pathology. (2006) [Pubmed]
  12. Monoclonal antibodies specific for canine CD4 and CD8 define functional T-lymphocyte subsets and high-density expression of CD4 by canine neutrophils. Moore, P.F., Rossitto, P.V., Danilenko, D.M., Wielenga, J.J., Raff, R.F., Severns, E. Tissue Antigens (1992) [Pubmed]
  13. Rhinitis/Bronchopneumonia syndrome in Irish Wolfhounds. Clercx, C., Reichler, I., Peeters, D., McEntee, K., German, A., Dubois, J., Schynts, E., Schaaf-Lafontaine, N., Willems, T., Jorissen, M., Day, M.J. J. Vet. Intern. Med. (2003) [Pubmed]
  14. Immunohistochemical detection of canine leucocyte antigens by specific monoclonal antibodies in canine normal tissues. Rabanal, R.M., Ferrer, L., Else, R.W. Vet. Immunol. Immunopathol. (1995) [Pubmed]
  15. Primary structure of the canine CD4 antigen. Milde, K.F., Conner, G.E., Mintz, D.H., Alejandro, R. Biochim. Biophys. Acta (1993) [Pubmed]
  16. CD4 and CD8 monoclonal antibody therapy in canine renal allografts. Watson, C.J., Cobbold, S.P., Davies, H.F., Rebello, P.R., Waldmann, H., Calne, R.Y., Metcalfe, S.M. Transpl. Int. (1994) [Pubmed]
  17. CD4 and CD8 monoclonal antibody therapy: strategies to prolong renal allograft survival in the dog. Watson, C.J., Cobbold, S.P., Davies, H.S., Rebello, P.R., Waldmann, H., Calne, R.Y., Metcalfe, S.M. The British journal of surgery. (1993) [Pubmed]
  18. Response to Malassezia pachydermatis by peripheral blood mononuclear cells from clinically normal and atopic dogs. Morris, D.O., Clayton, D.J., Drobatz, K.J., Felsburg, P.J. Am. J. Vet. Res. (2002) [Pubmed]
  19. Pradimicin S, a new pradimicin analog. I. Taxonomy, fermentation and biological activities. Saitoh, K., Tenmyo, O., Yamamoto, S., Furumai, T., Oki, T. J. Antibiot. (1993) [Pubmed]
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