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Gene Review

Cd28  -  CD28 antigen

Mus musculus

Synonyms: T-cell-specific surface glycoprotein CD28
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Disease relevance of Cd28

  • Interestingly, the ability to control the first parasitemia peak was not compromised in acutely infected CD28(-/-) mice, but CD28(-/-) mice failed to eradicate the parasites that persisted in the blood for >3 mo after infection [1].
  • Contact hypersensitivity to dinitrofluorobenzene and oxazolone was significantly decreased in CD28 -/- mice compared with that in normal (C57BL/6) mice [2].
  • These results indicate that the CD28 molecule is required not only for optimal induction of allergic contact dermatitis, but also for the development of irritant-induced skin inflammation [2].
  • Fifteen mice with Pasteurella pneumotropica orbital abscesses were noted in mice that were homozygous for a targeted Cd28 gene mutation [3].
  • By contrast, animals lacking the T cell-costimulatory molecule CD28 (CD28 -/-) developed autoimmune heart disease, although at significantly lower severity than in heterozygous littermates, and produced IgG auto-Abs depending on the concentration of the autoantigen administered [4].

High impact information on Cd28

  • CD3-specific antibody treatment induced remission in NOD Cd28-/- mice that were devoid of such regulatory cells [5].
  • Pax5-repressed genes are also reexpressed in plasma cells, which depend for normal function on Cd28 and Ccr2 reactivation [6].
  • BALB/c CD28-/- mice developed high levels of IL-4 mRNA and protein induction in the draining lymph nodes [7].
  • Diverse factors including costimulatory signals, genetic polymorphism, and the nature of the immunogen all influence T helper phenotype commitment, but these results provide evidence that CD28 is not an absolute requirement for generating either Th1 or Th2 responses [7].
  • We also activated transgenic CD28-bearing T cells from the BALB and C57BL background in vitro in the presence of CTLA4Ig [7].

Biological context of Cd28

  • Cd28 and Ctla-4, two related members of the Ig supergene family, are tightly linked on proximal mouse chromosome 1 [8].
  • In contrast, CD152 signals are not required for the maintenance of established graft survival [9].
  • Although CD40L(-/-) mice failed to control infection, CD28(-/-) and CD40L(-/-)CD28(-/-) mice, as well as C57BL/6 mice, spontaneously resolved their infections [10].
  • We additionally find that blockade of CD152 at the time of transplantation does not interfere with the effectiveness of anti-CD154 mAbs, suggesting distinct mechanisms for inhibition of graft rejection by blocking the CD28 vs CD154 pathways [9].
  • Induction of autoimmunity in the absence of CD28 costimulation [4].

Anatomical context of Cd28

  • In addition, drug-cured CD28(-/-) mice were unable to generate memory T cells, develop an anamnesic IgG response, or eliminate the parasites from a secondary challenge [1].
  • Role of CD28 in polyclonal and specific T and B cell responses required for protection against blood stage malaria [1].
  • The role of CD28-mediated signals in T helper cell maturation is not fully understood [7].
  • In contrast, in H. polygyrus-challenged CD28(-/-) mice, marked elevations in Ag-specific IgG1 and IgE and increased germinal center formation were observed [11].

Associations of Cd28 with chemical compounds

  • Significant increases in IL-2 mRNA were detected in the skin after dinitrofluorobenzene challenge in normal mice, while this response was blunted in CD28 -/- mice [2].
  • In addition, responses to irritant chemicals (croton oil and phenol) were also impaired in CD28 -/- mice [2].

Other interactions of Cd28

  • The newly defined gene cannot be dissociated from Ctla4 and Cd28 and in fact marks a 20-centimorgan region encompassing Idd5, a previously postulated diabetes susceptibility locus [12].
  • However, humoral immunity is impaired and differentially affected in B7-1/B7-2(-/-) mice and CD28(-/-) mice following H. polygyrus challenge [11].
  • Bispecific monoclonal antibodies (Bi-mAbs) specific for a tumor-associated antigen and the CD3 or CD28 antigen on T lymphocytes represent one of the most successful experimental strategies for the immunotherapy of cancer [13].
  • As opposed to WT, CD28(-/-) showed a greatly attenuated increase in plasma KC 4 h after LPS (2.5- versus 138.5-fold over controls, respectively) [14].
  • The CD28 antigen has been recently demonstrated to be a costimulatory molecule and is expressed by almost all thymic and peripheral T cell receptor (TcR) alpha beta+ and gamma delta+ cells in the mouse system [15].

Analytical, diagnostic and therapeutic context of Cd28

  • Moreover, reinfected CD28(-/-) mice were protected by the adoptive transfer of serum from reinfected CD28(+/+) mice containing specific IgG2a [1].
  • This requires that anti-CD86 mAb is given on the day of transplantation and also depends upon an intact CD152 pathway [9].
  • Here, we show that blockade of CD152 using an anti-CD152 mAb at the time of transplantation prevents the induction of long-term allograft survival by agents that target CD80 and CD86 [9].
  • T cells from CD28 -/- mice did not bind to epidermal cells derived from normal mice, while cocultivation of T cells with epidermal cells from normal mice demonstrated a significant binding [2].
  • Flow cytometry demonstrated that CD28 was vastly expressed on CD3(+) cells but not on PMN [14].


  1. Role of CD28 in polyclonal and specific T and B cell responses required for protection against blood stage malaria. Elias, R.M., Sardinha, L.R., Bastos, K.R., Zago, C.A., da Silva, A.P., Alvarez, J.M., Lima, M.R. J. Immunol. (2005) [Pubmed]
  2. Contribution of the CD28 molecule to allergic and irritant-induced skin reactions in CD28 -/- mice. Kondo, S., Kooshesh, F., Wang, B., Fujisawa, H., Sauder, D.N. J. Immunol. (1996) [Pubmed]
  3. Outbreak of Pasteurella pneumotropica in a closed colony of STOCK-Cd28(tm1Mak) mice. Artwohl, J.E., Flynn, J.C., Bunte, R.M., Angen, O., Herold, K.C. Contemporary topics in laboratory animal science / American Association for Laboratory Animal Science. (2000) [Pubmed]
  4. Induction of autoimmunity in the absence of CD28 costimulation. Bachmaier, K., Pummerer, C., Shahinian, A., Ionescu, J., Neu, N., Mak, T.W., Penninger, J.M. J. Immunol. (1996) [Pubmed]
  5. TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes. Belghith, M., Bluestone, J.A., Barriot, S., Mégret, J., Bach, J.F., Chatenoud, L. Nat. Med. (2003) [Pubmed]
  6. Gene repression by Pax5 in B cells is essential for blood cell homeostasis and is reversed in plasma cells. Delogu, A., Schebesta, A., Sun, Q., Aschenbrenner, K., Perlot, T., Busslinger, M. Immunity (2006) [Pubmed]
  7. Limited role of CD28-mediated signals in T helper subset differentiation. Brown, D.R., Green, J.M., Moskowitz, N.H., Davis, M., Thompson, C.B., Reiner, S.L. J. Exp. Med. (1996) [Pubmed]
  8. Cd28 and Ctla-4, two related members of the Ig supergene family, are tightly linked on proximal mouse chromosome 1. Howard, T.A., Rochelle, J.M., Seldin, M.F. Immunogenetics (1991) [Pubmed]
  9. The role of CD80, CD86, and CTLA4 in alloimmune responses and the induction of long-term allograft survival. Judge, T.A., Wu, Z., Zheng, X.G., Sharpe, A.H., Sayegh, M.H., Turka, L.A. J. Immunol. (1999) [Pubmed]
  10. The development of a Th1-type response and resistance to Leishmania major infection in the absence of CD40-CD40L costimulation. Padigel, U.M., Perrin, P.J., Farrell, J.P. J. Immunol. (2001) [Pubmed]
  11. Memory Th2 effector cells can develop in the absence of B7-1/B7-2, CD28 interactions, and effector Th cells after priming with an intestinal nematode parasite. Ekkens, M.J., Liu, Z., Liu, Q., Foster, A., Whitmire, J., Pesce, J., Sharpe, A.H., Urban, J.F., Gause, W.C. J. Immunol. (2002) [Pubmed]
  12. Apoptosis resistance of nonobese diabetic peripheral lymphocytes linked to the Idd5 diabetes susceptibility region. Colucci, F., Bergman, M.L., Penha-Gonçalves, C., Cilio, C.M., Holmberg, D. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  13. Immunotherapy of human tumors with T-cell-activating bispecific antibodies: stimulation of cytotoxic pathways in vivo. Bauer, S., Renner, C., Juwana, J.P., Held, G., Ohnesorge, S., Gerlach, K., Pfreundschuh, M. Cancer Res. (1999) [Pubmed]
  14. T cells modulate neutrophil-dependent acute renal failure during endotoxemia: critical role for CD28. Singbartl, K., Bockhorn, S.G., Zarbock, A., Schmolke, M., Van Aken, H. J. Am. Soc. Nephrol. (2005) [Pubmed]
  15. Expression of the CD28 costimulatory molecule on subsets of murine intestinal intraepithelial lymphocytes correlates with lineage and responsiveness. Ohteki, T., MacDonald, H.R. Eur. J. Immunol. (1993) [Pubmed]
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