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Gene Review

CD4  -  CD4 molecule

Sus scrofa

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Disease relevance of CD4

  • The cytoprotective action of TMZ also reduced interstitial fibrosis and the numbers of infiltrating CD4- and CD8-positive cells [1].
  • METHODS: The effect of targeting CD4 by nondepleting anti-CD4 monoclonal antibodies (mAbs) versus blocking CD28/B7 by CTLA4Ig, anti-CD80 mAbs, and anti-CD86 mAbs on the prevention of recurrence of autoimmune diabetes after MHC-matched nonobese diabetes-resistant (NOR) islet transplantation in nonobese diabetic (NOD) mice were compared [2].
  • In pulmonary genetic diseases, such as emphysema and cystic fibrosis, proteases can also favour the development of local immunodeficiency by degrading key regulators of the immune response, such as CD4, CD8, IgG, ICAM-1 and C3b receptors [3].
  • METHODS: Immunoglobulin single chain variable domain fragments of a murine monoclonal antibody with specificity for rat CD4 were engineered with a 20 or 11 amino acid linker by assembly polymerase chain reaction, expressed in Escherichia coli and purified by chromatography [4].
  • At different times after reconstitution, enriched CD4 and CD45 positive porcine cells were isolated from various mouse organs and tested for the presence of porcine NIPC by porcine IFN-alpha specific ELISPOT assay, after in vitro stimulation by UV inactivated transmissible gastroenteritis virus (TGEV) [5].

High impact information on CD4

  • These experiments suggest that CD4 may be important in determining the antigen fine specificity and, therefore, may also play a role in altering the T cell repertoire [6].
  • We have transfected the mouse CD4 gene into a beef insulin (BI)-specific murine T helper hybridoma that lacks CD4 surface expression [6].
  • To address the role of CD4 in this mechanism, we studied the interactions of the anti-CD4 mAb W3/25 with an encephalitogenic line of T helper cells [7].
  • Function of the CD4 subset in vivo, as demonstrated by antibody production against a T cell-dependent Ag, is similar between animals of both phenotypes [8].
  • CD4 allelism is confirmed by Southern blot analysis, revealing RFLP [8].

Chemical compound and disease context of CD4


Biological context of CD4

  • Although the polymorphism includes differences in exons 3 and 4, regions thought to encode portions of the molecule interacting with MHC class II, these results imply that this naturally occurring CD4 polymorphism does not affect the interaction with class II molecules [8].
  • While there are several studies describing the nature of the pathologic response in primate, guinea pig, and murine models, there is less information on the kinetics of the CD4 and CD8 response following primary and challenge infections [9].
  • Epithelial damage and obliteration were graded histologically, and the number of CD4, CD8, MHC class II expressing cells, macrophages, and B lymphocytes were counted (mean+SEM)/high-power visual field [10].
  • Light microscopic studies were undertaken to immunophenotype the immunologic response using specific antibodies to T-cell subsets (CD3, CD4, and CD8), B cells, major histocompatibility complex class II, cadherin, and macrophages over the course of time [11].
  • Peripheral blood leukocytes were scanned for donor chimerism and CD3, CD4, CD8 and CD25 expression [12].

Anatomical context of CD4

  • The majority of infiltrating lymphocytes were CD4-positive in control mice but CD8-positive in IgKO mice [13].
  • Tissues from individual animals were assessed for cells expressing CD4, CD8, or Mac-1 and for B cells [9].
  • Monoclonal antibodies directed against the CD4 or CD8 markers on guinea pig lymphocytes were used in a flow cytofluorometric assay to determine the proportion of each subset in the peripheral circulation, spleen, and bronchotracheal lymph nodes at 4 weeks after infection [14].
  • Graft sizes and number of infiltrating CD4- and CD8-positive lymphocytes were determined by stereological methods at 4 days and 2, 4, and 6 weeks after the transplants [13].
  • Twenty-one days after challenge infection, which was performed 50 days after the primary infection, there was a significant increase in the number of CD4, CD8, and B cells in the oviduct compared to the number of these cells at the same time after a primary infection, providing clear cellular evidence for a cell-mediated immune pathologic response [9].

Associations of CD4 with chemical compounds


Regulatory relationships of CD4

  • Single stainings showed that cells positive for the CD2 and CD8 antigen were almost as numerous in pneumonic lesions as CD3 positive cells whereas cells expressing the CD4 antigen were rare [17].
  • The remaining perforin positive lymphocytes were large and granular and contained more CD3+CD5+CD6+ T-cells (-40%) of which a substantial proportion also co-expressed CD4 [18].

Other interactions of CD4

  • Results indicate that the percentages of Class I, Class II, CD3, CD8, CD4, CD45, monocyte, gamma-delta T-cell populations, and total number of granulocytes identified using this method were comparable to standard values or to values obtained following separation of white blood cells from red blood cells [19].
  • The p180+ T cells have a distribution in lymphoid tissues that is distinct from that of T cells that express the CD2, CD4 or CD8 molecules [20].
  • Vaccination prevented an increase in C-reactive protein serum levels, general activation of CD4 and CD8 subsets and boosted development of humoral and cellular immune responses to a spectrum of mycobacterial antigens on exposure to M. tuberculosis infection [21].
  • However, by the mid-stage of the cycle there was a significant and dramatic fall in CD2+ T cells and other lymphocytes expressing the CD4, CD8 and CD1 phenotypes, MHC class II+ cells were predominant throughout the endometrium [22].
  • Tissue sections were stained for the T-cell markers CD2, CD3 gamma delta, CD4 and CD8, for the B-cell markers IgM, IgA and IgG, for a macrophage marker, and for PRV antigen [23].

Analytical, diagnostic and therapeutic context of CD4

  • Northern blot analysis confirms the presence of mRNA for CD4 among PBL of animals failing to stain with 74-12-4 [8].
  • RESULTS: After T-cell depletion and thymic transplantation, recovery of thymus-dependent naïve-type CD4 cells (CD4/CD45RA ) and in vitro xenogeneic hyporesponsiveness were observed [24].
  • Flow cytometry analyses showed that the mAb recognized a subset of T lymphocytes of which the majority expressed no CD2, CD4 and CD8 whilst the minority bore CD2 and CD8 [25].
  • CD3 cells decreased in all groups, but CD4 and CD8 cells decreased only in the resuscitation groups [26].
  • There was no evidence of an immune response to the venous homografts, as judged by staining for T-cell surface antigen, CD4, and CD8 [27].


  1. Influence of cold-storage conditions on renal function of autotransplanted large pig kidneys. Goujon, J.M., Vandewalle, A., Baumert, H., Carretier, M., Hauet, T. Kidney Int. (2000) [Pubmed]
  2. Immunotherapy with nondepleting anti-CD4 monoclonal antibodies but not CD28 antagonists protects islet graft in spontaneously diabetic nod mice from autoimmune destruction and allogeneic and xenogeneic graft rejection. Guo, Z., Wu, T., Kirchhof, N., Mital, D., Williams, J.W., Azuma, M., Sutherland, D.E., Hering, B.J. Transplantation (2001) [Pubmed]
  3. Increased proteolytic activity and matrix metalloprotease expression in lungs during infection by porcine reproductive and respiratory syndrome virus. Girard, M., Cléroux, P., Tremblay, P., Dea, S., St-Pierre, Y. J. Gen. Virol. (2001) [Pubmed]
  4. Influence of format on in vitro penetration of antibody fragments through porcine cornea. Brereton, H.M., Taylor, S.D., Farrall, A., Hocking, D., Thiel, M.A., Tea, M., Coster, D.J., Williams, K.A. The British journal of ophthalmology. (2005) [Pubmed]
  5. Absence of porcine interferon alpha secreting cells in severe combined immunodeficiency (SCID) mice inoculated with porcine leukocytes. Splíchal, I., Sinkora, J., Reháková, Z., Sinkora, M., Charley, B. Vet. Res. (1998) [Pubmed]
  6. Acquisition of an additional antigen specificity after mouse CD4 gene transfer into a T helper hybridoma. Ballhausen, W.G., Reske-Kunz, A.B., Tourvieille, B., Ohashi, P.S., Parnes, J.R., Mak, T.W. J. Exp. Med. (1988) [Pubmed]
  7. Autologous rat myelin basic protein is a partial agonist that is converted into a full antagonist upon blockade of CD4. Evidence for the integration of efficacious and nonefficacious signals during T cell antigen recognition. Mannie, M.D., Rosser, J.M., White, G.A. J. Immunol. (1995) [Pubmed]
  8. Characterization of a polymorphism of CD4 in miniature swine. Sundt, T.M., LeGuern, C., Germana, S., Smith, C.V., Nakajima, K., Lunney, J.K., Sachs, D.H. J. Immunol. (1992) [Pubmed]
  9. Characterization of lymphocyte response in the female genital tract during ascending Chlamydial genital infection in the guinea pig model. Rank, R.G., Bowlin, A.K., Kelly, K.A. Infect. Immun. (2000) [Pubmed]
  10. Immune cells and immunosuppression in a porcine bronchial model of obliterative bronchiolitis. Maasilta, P.K., Salminen, U.S., Lautenschlager, I.T., Taskinen, E.I., Harjula, A.L. Transplantation (2001) [Pubmed]
  11. Immunopathogenesis of experimentally induced proliferative enteropathy in pigs. MacIntyre, N., Smith, D.G., Shaw, D.J., Thomson, J.R., Rhind, S.M. Vet. Pathol. (2003) [Pubmed]
  12. Tacrolimus versus cyclosporine induction therapy in pulmonary transplantation in miniature swine. Warnecke, G., Avsar, M., Steinkamp, T., Reinhard, R., Niedermeyer, J., Simon, A.R., Haverich, A., Strüber, M. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. (2005) [Pubmed]
  13. Discordant neural tissue xenografts survive longer in immunoglobulin deficient mice. Larsson, L.C., Czech, K.A., Widner, H., Korsgren, O. Transplantation (1999) [Pubmed]
  14. Protein deficiency induces alterations in the distribution of T-cell subsets in experimental pulmonary tuberculosis. Mainali, E.S., McMurray, D.N. Infect. Immun. (1998) [Pubmed]
  15. A sub-population of circulating porcine gammadelta T cells can act as professional antigen presenting cells. Takamatsu, H.H., Denyer, M.S., Wileman, T.E. Vet. Immunol. Immunopathol. (2002) [Pubmed]
  16. Immunohistochemical detection of SWC3, CD2, CD3, CD4 and CD8 antigens in paraformaldehyde fixed and paraffin embedded porcine lymphoid tissue. Tingstedt, J.E., Tornehave, D., Lind, P., Nielsen, J. Vet. Immunol. Immunopathol. (2003) [Pubmed]
  17. Cellular immune responses in the lungs of pigs infected in utero with PRRSV: an immunohistochemical study. Tingstedt, J.E., Nielsen, J. Viral Immunol. (2004) [Pubmed]
  18. Perforin expression can define CD8 positive lymphocyte subsets in pigs allowing phenotypic and functional analysis of natural killer, cytotoxic T, natural killer T and MHC un-restricted cytotoxic T-cells. Denyer, M.S., Wileman, T.E., Stirling, C.M., Zuber, B., Takamatsu, H.H. Vet. Immunol. Immunopathol. (2006) [Pubmed]
  19. A simple and rapid flow cytometric method for detection of porcine cell surface markers. Stabel, T.J., Bolin, S.R., Pesch, B.A., Rahner, T.E. J. Immunol. Methods (2000) [Pubmed]
  20. Expression on porcine gamma delta lymphocytes of a phylogenetically conserved surface antigen previously restricted in expression to ruminant gamma delta T lymphocytes. Carr, M.M., Howard, C.J., Sopp, P., Manser, J.M., Parsons, K.R. Immunology (1994) [Pubmed]
  21. Protection of macaques against Mycobacterium tuberculosis infection by a subunit vaccine based on a fusion protein of antigen 85B and ESAT-6. Langermans, J.A., Doherty, T.M., Vervenne, R.A., van der Laan, T., Lyashchenko, K., Greenwald, R., Agger, E.M., Aagaard, C., Weiler, H., van Soolingen, D., Dalemans, W., Thomas, A.W., Andersen, P. Vaccine (2005) [Pubmed]
  22. Studies on the distribution of immune cells in the uteri of prepubertal and cycling gilts. Bischof, R.J., Brandon, M.R., Lee, C.S. J. Reprod. Immunol. (1994) [Pubmed]
  23. Immunohistological characterization of the local cellular response directed against pseudorabies virus in pigs. Bouma, A., Zwart, R.J., De Bruin, M.G., De Jong, M.C., Kimman, T.G., Bianchi, A.T. Vet. Microbiol. (1997) [Pubmed]
  24. Xenogeneic thymus transplantation in a pig-to-baboon model. Wu, A., Yamada, K., Neville, D.M., Awwad, M., Wain, J.C., Shimizu, A., Gojo, S., Kitamura, H., Colvin, R.B., Cooper, D.K., Sykes, M., Sachs, D.H. Transplantation (2003) [Pubmed]
  25. Characterization of the porcine gammadelta T-cell receptor structure and cellular distribution by monoclonal antibody PPT27. Yang, H., Parkhouse, R.M. Immunology (2000) [Pubmed]
  26. Immune effects of resuscitation with HBOC-201, a hemoglobin-based oxygen carrier, in swine with moderately severe hemorrhagic shock from controlled hemorrhage. Dong, F., Hall, C.H., Golech, S.A., Philbin, N.B., Rice, J.P., Gurney, J., Arnaud, F.G., Hammett, M., Ma, X., Flournoy, W.S., Hong, J., Kaplan, L.J., Pearce, L.B., McGwin, G., Ahlers, S., McCarron, R., Freilich, D. Shock (2006) [Pubmed]
  27. Depopulated vena caval homograft: a new venous conduit. Wells, W., Malas, M., Baker, C.J., Quardt, S.M., Barr, M.L. J. Thorac. Cardiovasc. Surg. (2003) [Pubmed]
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