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Gene Review

Ctla4  -  cytotoxic T-lymphocyte-associated protein 4

Rattus norvegicus

Synonyms: CTLA-4, Cd152, sCTLA4
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Disease relevance of Ctla4

  • Blockade of CD40 ligand suppresses chronic experimental myasthenia gravis by down-regulation of Th1 differentiation and up-regulation of CTLA-4 [1].
  • METHODS: Uninephrectomized rats were submitted to warm renal ischemia (30 min) and received control monoclonal antibody (mAb; 17E3), anti-B7-1 (3H5), anti-B7-2 (24F), a combination of anti-B7-1/B7-2, or CTLA-4 Ig [2].

High impact information on Ctla4

  • T-cell costimulation is provided by ligation of CD28 with either B7.1 (CD80) or B7.2 (CD86) on antigen-presenting cells, and can be inhibited by a soluble form of CTLA4 (CTLA4-Ig) that binds to both B7.1 and B7 [3].
  • Treatment with a diet deficient in essential fatty acids (which attenuates arteriosclerosis) or CTLA-4 Ig (which blocks lymphocyte activation) significantly decreased AIF-1 transcript levels [4].
  • In addition, a short course of cyclosporine therapy synergized with either anti-CD28 monoclonal antibody or CTLA4 immunoglobulin, suggesting that it may be clinically relevant to combine low-dose calcineurin inhibitors with CTLA4 immunoglobulin or anti-B7 antibodies [5].
  • BACKGROUND: Blocking the costimulatory pathway by CTLA-4 Ig, reactive with both B7-1 and B7-2 costimulatory molecules, protects the kidney during acute ischemia/reperfusion injury [2].
  • BACKGROUND: CTLA4 immunoglobulin (Ig)G that binds to B7 effectively inhibits the signaling of CD28/CTLA4-B7 pathway and induces antigen specific T cell unresponsiveness in vitro and in vivo [6].

Biological context of Ctla4


Anatomical context of Ctla4

  • CTLA4Ig is a recombinant soluble protein that binds with high affinity to rat B7/BB1 and other surface molecules on APCs, subsequently blocking the binding of B7/BB1 to CD28/CTLA4 on T cells [10].
  • In addition, cytotoxic T lymphocyte antigen 4 (CTLA4/CD152), which may function as an immune attenuator, was strongly stained, and B7 was weakly stained in recipient liver in the PV group compared with the IV group [11].

Analytical, diagnostic and therapeutic context of Ctla4

  • We demonstrated that anti-CD28 monoclonal antibody was as effective as CTLA4 immunoglobulin in protecting against chronic allograft vasculopathy [5].
  • RESULTS: CTLA4 protein was detected on postoperative days 5, 9 and 14, with liver graft tissue transduction indexes of 7.2, 10.9 and 1.8, respectively [12].
  • Adenovirus-mediated CTLA4 immunoglobulin G gene therapy in cardiac xenotransplantation [13].


  1. Blockade of CD40 ligand suppresses chronic experimental myasthenia gravis by down-regulation of Th1 differentiation and up-regulation of CTLA-4. Im, S.H., Barchan, D., Maiti, P.K., Fuchs, S., Souroujon, M.C. J. Immunol. (2001) [Pubmed]
  2. Anti-B7-1 blocks mononuclear cell adherence in vasa recta after ischemia. De Greef, K.E., Ysebaert, D.K., Dauwe, S., Persy, V., Vercauteren, S.R., Mey, D., De Broe, M.E. Kidney Int. (2001) [Pubmed]
  3. CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis. Reynolds, J., Tam, F.W., Chandraker, A., Smith, J., Karkar, A.M., Cross, J., Peach, R., Sayegh, M.H., Pusey, C.D. J. Clin. Invest. (2000) [Pubmed]
  4. Cloning and characterization of allograft inflammatory factor-1: a novel macrophage factor identified in rat cardiac allografts with chronic rejection. Utans, U., Arceci, R.J., Yamashita, Y., Russell, M.E. J. Clin. Invest. (1995) [Pubmed]
  5. Mechanisms of targeting CD28 by a signaling monoclonal antibody in acute and chronic allograft rejection. Dong, V.M., Yuan, X., Coito, A.J., Waaga, A.M., Sayegh, M.H., Chandraker, A. Transplantation (2002) [Pubmed]
  6. CTLA4IgG treatment induces long-term acceptance of rat small bowel allografts. Tarumi, K., Murakami, M., Yagihashi, A., Nakagawa, I., Hirata, K., Uede, T. Transplantation (1999) [Pubmed]
  7. Nucleotide sequence of the ACI rat CTLA-4 molecule. Oaks, M.K., Penwell, R.T., Tector, A.J. Immunogenetics (1996) [Pubmed]
  8. Suppression of experimental myasthenia gravis, a B cell-mediated autoimmune disease, by blockade of IL-18. Im, S.H., Barchan, D., Maiti, P.K., Raveh, L., Souroujon, M.C., Fuchs, S. FASEB J. (2001) [Pubmed]
  9. Local or short-term systemic costimulatory molecule blockade prolongs rat corneal allograft survival. Thiel, M.A., Steiger, J.U., O'Connell, P.J., Lehnert, A.M., Coster, D.J., Williams, K.A. Clin. Experiment. Ophthalmol. (2005) [Pubmed]
  10. Soluble CTLA4Ig modifies parameters of acute inflammation in rat lung allograft rejection without altering lymphocytic infiltration or transcription of key cytokines. Matsumura, Y., Zuo, X.J., Prehn, J., Linsley, P.S., Marchevsky, A., Kass, R.M., Matloff, J.M., Jordan, S.C. Transplantation (1995) [Pubmed]
  11. Donor dendritic cells and recipient Kupffer cells in the induction of donor-specific immune hyporesponsiveness. Nakagawa, K., Matsuno, T., Iwagaki, H., Morimoto, Y., Fujiwara, T., Sadamori, H., Inagaki, M., Urushihara, N., Yagi, T., Tanaka, N. J. Int. Med. Res. (2001) [Pubmed]
  12. Liver as an ideal target for gene therapy: expression of CTLA4Ig by retroviral gene transfer. Cheung, S.T., Tsui, T.Y., Wang, W.L., Yang, Z.F., Wong, S.Y., Ip, Y.C., Luk, J., Fan, S.T. J. Gastroenterol. Hepatol. (2002) [Pubmed]
  13. Adenovirus-mediated CTLA4 immunoglobulin G gene therapy in cardiac xenotransplantation. Watanabe, T., Miyatake, T., Kumamoto, H., Mafune, N., Kubota, S., Okamoto, H., Murashita, T., Uede, T., Yasuda, K. Transplant. Proc. (2004) [Pubmed]
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