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Gene Review

CD4  -  CD4 molecule

Gallus gallus

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Disease relevance of CD4

  • CD4 cells were least tolerant in TCR/thyroid-HEL and TCR/islet-HEL mice, which developed an extensive lymphocytic thyroiditis or insulitis that nevertheless did not eliminate HEL-expressing endocrine cells [1].
  • A range of CD4 T cell tolerance: partial inactivation to organ-specific antigen allows nondestructive thyroiditis or insulitis [1].
  • Autoreactive CD4 clones thus escape the thymus under a range of circumstances, retain sufficient function to initiate subclinical autoimmune inflammation when self-antigens are concentrated in the thyroid or pancreas, and may regulate progression of subclinical inflammation to destructive autoimmune disease [1].
  • Shortened survival was associated with low CD4 lymphocyte count (P<.0001), no ART (P<.0001), and cryptosporidiosis (P=.004) but not with microsporidiosis (P=.48) [2].
  • CD4, CD8, TCR1, TCR2, and TCR3 subsets of T cells and B cells were present in the outer rim of the granuloma/lymphocyte aggregates [3].

Psychiatry related information on CD4

  • Of 2652 patients, 66% were male, 6% received antiretroviral therapy (ART), and the median CD4 lymphocyte count was 131 cells/microL [2].

High impact information on CD4

  • CN OVA-specific effectors were also CD8+, CD4-, but surprisingly, were able to lyse a range of H-2-different targets in an antigen-specific manner [4].
  • Interestingly, there are no Ser residues in the cytoplasmic part, which may explain the slow down-regulation of chicken CD4 after phorbol ester stimulation [5].
  • We have cloned and sequenced the first nonmammalian CD4 cDNA from the chicken using the COS cell expression method [5].
  • Molecular modeling also implies that the membrane-proximal domain mediates dimerization of chicken CD4 in a similar way as it does for human CD4 [5].
  • Chicken CD4 contains four extracellular Ig domains that, in analogy to mammalian CD4, are in the order V, C2, V, and C2 [5].

Biological context of CD4


Anatomical context of CD4

  • The TCR2+ cells (alpha beta TCR homologue), a majority of which express the CD4 homologue, are found primarily in the splenic periarteriolar sheath and the lamina propria of the intestine [9].
  • A panel of murine mAb specific for the chicken homologues of the CD3, CD4, CD8, TCR gamma delta, and TCR alpha beta has been used to study the distribution of T cells expressing these markers in sections of chicken lymphoid tissues [9].
  • Since quail cells are not recognized by our panel of monoclonal antibodies against chicken TcR1, TcR2, TcR3, CD3, CD4 and CD8 molecules, these antibodies provided reliable markers for donor chick lymphocytes in the tissues of the quail recipients [10].
  • We present an expression/selection system designed for the purification of cell lines inducibly expressing genes coding for unselectable proteins by using dicistronic selection for the cell surface marker CD4 [11].
  • Lymphocyte markers included fluorescence-conjugated monoclonal antibodies to identify T cells (CD3), T helper cells (CD4), cytotoxic T cells (CD8), and B cells (IgM) [12].

Associations of CD4 with chemical compounds

  • This identity included a glycine residue at position 2 (present in all Scr-related tyrosine protein kinases) and a cysteine motif at positions 20 and 23, which allows binding of p56lck to CD4 and CD8 in mammalian T lymphocytes [13].
  • This paper introduces a transgenic (Tg) mouse in which the majority of the CD4-bearing T cells have T-cell receptors that react with ovalbumin (OVA) as a model for ethanol research [14].
  • FK 506 and cyclosporin each block antigen-induced T cell receptor signalling that is dependent on CD4 co-receptor and operates in the absence of detectable cytoplasmic calcium fluxes [15].
  • Birds on the PROB diet had more IEL expressing the surface markers CD3, CD4, CD8, and alphabetaTCR than those of the CONT diet [16].
  • Effects of dietary vitamin E on the immune system in broilers: altered proportions of CD4 T cells in the thymus and spleen [17].

Physical interactions of CD4


Other interactions of CD4

  • UA04 cells express CD3low, CD4, TCR-2low, MHC class II, and CD28 antigens on their surface [19].
  • The results presented in this report demonstrate that the avian CD4 and CD8 homologs are physically associated with a cellular tyrosine protein kinase related to mammalian p56lck [18].
  • These results indicate that (a) mAb CTLA5 and 8 identify antigens on mature T lymphocytes that are similar in tissue distribution, molecular mass and function to the mammalian CD5 antigen; (b) mAb CTLA3, 4 and 9 detect the avian homologue of CD8 antigen; and (c) mAb CTLA1 and 6 identify the avian homologue of CD4 antigen [20].
  • Monoclonal antibodies and antisera against leucocytes, T lymphocytes, CD4, B lymphocytes, mononuclear phagocytes, MHC class II, and keratin were used [21].

Analytical, diagnostic and therapeutic context of CD4

  • To further define the relationship between thymocyte subsets and their developmental sequence, multi-parameter flow cytometry was used to determine the distribution of the CD3-TCR complex and the accessory molecules CD4 and CD8 on chicken thymocytes [22].
  • CTL lines generated via oral administration of antigen were shown to be CD3(+), CD4(-), and CD8(+) [23].
  • Immune organ weights, circulating granulocytes vs. agranulocytes, CD4 and CD8 positive T cells, cutaneous basophil hypersensitivity, and antibody titers to SRBC and breeder vaccinations were measured in progeny [24].


  1. A range of CD4 T cell tolerance: partial inactivation to organ-specific antigen allows nondestructive thyroiditis or insulitis. Akkaraju, S., Ho, W.Y., Leong, D., Canaan, K., Davis, M.M., Goodnow, C.C. Immunity (1997) [Pubmed]
  2. The epidemiology of intestinal microsporidiosis in patients with HIV/AIDS in Lima, Peru. Bern, C., Kawai, V., Vargas, D., Rabke-Verani, J., Williamson, J., Chavez-Valdez, R., Xiao, L., Sulaiman, I., Vivar, A., Ticona, E., Navincopa, M., Cama, V., Moura, H., Secor, W.E., Visvesvara, G., Gilman, R.H. J. Infect. Dis. (2005) [Pubmed]
  3. Pulmonary and hematological inflammatory responses to intravenous cellulose micro-particles in broilers. Wang, W., Wideman, R.F., Bersi, T.K., Erf, G.F. Poult. Sci. (2003) [Pubmed]
  4. Induction of cytotoxic T lymphocytes by primary in vitro stimulation with peptides. Carbone, F.R., Moore, M.W., Sheil, J.M., Bevan, M.J. J. Exp. Med. (1988) [Pubmed]
  5. Cloning and modeling of the first nonmammalian CD4. Koskinen, R., Lamminmäki, U., Tregaskes, C.A., Salomonsen, J., Young, J.R., Vainio, O. J. Immunol. (1999) [Pubmed]
  6. The chicken CD4 gene has remained conserved in evolution. Koskinen, R., Salomonsen, J., Tregaskes, C.A., Young, J.R., Goodchild, M., Bumstead, N., Vainio, O. Immunogenetics (2002) [Pubmed]
  7. High levels of CD45 are coordinately expressed with CD4 and CD8 on avian thymocytes. Paramithiotis, E., Tkalec, L., Ratcliffe, M.J. J. Immunol. (1991) [Pubmed]
  8. Characterization of avian natural killer cells and their intracellular CD3 protein complex. Göbel, T.W., Chen, C.L., Shrimpf, J., Grossi, C.E., Bernot, A., Bucy, R.P., Auffray, C., Cooper, M.D. Eur. J. Immunol. (1994) [Pubmed]
  9. Avian T cells expressing gamma delta receptors localize in the splenic sinusoids and the intestinal epithelium. Bucy, R.P., Chen, C.L., Cihak, J., Lösch, U., Cooper, M.D. J. Immunol. (1988) [Pubmed]
  10. Cytoplasmic CD3+ surface CD8+ lymphocytes develop as a thymus-independent lineage in chick-quail chimeras. Bucy, R.P., Coltey, M., Chen, C.I., Char, D., Le Douarin, N.M., Cooper, M.D. Eur. J. Immunol. (1989) [Pubmed]
  11. Dicistronic selection for nuclear proteins in living animal cells. Smarda, J., Lipsick, J.S. Gene (1993) [Pubmed]
  12. Alterations in blood leukocyte populations in Smyth line chickens with autoimmune vitiligo. Erf, G.F., Smyth, J.R. Poult. Sci. (1996) [Pubmed]
  13. tkl is the avian homolog of the mammalian lck tyrosine protein kinase gene. Chow, L.M., Ratcliffe, M.J., Veillette, A. Mol. Cell. Biol. (1992) [Pubmed]
  14. Ethanol ingestion inhibits cell-mediated immune responses of unprimed T-cell receptor transgenic mice. Schodde, H., Hurst, S., Munroe, M., Barrett, T., Waltenbaugh, C. Alcohol. Clin. Exp. Res. (1996) [Pubmed]
  15. FK 506 and cyclosporin each block antigen-induced T cell receptor signalling that is dependent on CD4 co-receptor and operates in the absence of detectable cytoplasmic calcium fluxes. Metcalfe, S., Alexander, D., Turner, J. Transpl. Int. (1994) [Pubmed]
  16. Enhanced mucosal immunity against Eimeria acervulina in broilers fed a Lactobacillus-based probiotic. Dalloul, R.A., Lillehoj, H.S., Shellem, T.A., Doerr, J.A. Poult. Sci. (2003) [Pubmed]
  17. Effects of dietary vitamin E on the immune system in broilers: altered proportions of CD4 T cells in the thymus and spleen. Erf, G.F., Bottje, W.G., Bersi, T.K., Headrick, M.D., Fritts, C.A. Poult. Sci. (1998) [Pubmed]
  18. Avian CD4 and CD8 interact with a cellular tyrosine protein kinase homologous to mammalian p56lck. Veillette, A., Ratcliffe, M.J. Eur. J. Immunol. (1991) [Pubmed]
  19. Establishment of a lymphoblastoid cell line using a mutant MDV containing a green fluorescent protein expression cassette. Dienglewicz, R.L., Parcells, M.S. Acta Virol. (1999) [Pubmed]
  20. Functional and biochemical characterizations of avian T lymphocyte antigens identified by monoclonal antibodies. Lillehoj, H.S., Lillehoj, E.P., Weinstock, D., Schat, K.A. Eur. J. Immunol. (1988) [Pubmed]
  21. Transient depletion of cortical thymocytes induced by chicken anaemia agent. Jeurissen, S.H., Pol, J.M., de Boer, G.F. Thymus (1989) [Pubmed]
  22. Delineation of chicken thymocytes by CD3-TCR complex, CD4 and CD8 antigen expression reveals phylogenically conserved and novel thymocyte subsets. Davidson, N.J., Boyd, R.L. Int. Immunol. (1992) [Pubmed]
  23. Oral immunization with enterocoated microbeads induces antigen-specific cytolytic T-cell responses. Vogel, K., Kantor, J., Wood, L., Rivera, R., Schlom, J. Cell. Immunol. (1998) [Pubmed]
  24. Immune system and cardiac functions of progeny chicks from dams fed diets differing in zinc and manganese level and source. Virden, W.S., Yeatman, J.B., Barber, S.J., Willeford, K.O., Ward, T.L., Fakler, T.M., Wideman, R.F., Kidd, M.T. Poult. Sci. (2004) [Pubmed]
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