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

• Nucleotide sequence of the ACI rat CTLA-4 molecule [7].
• Suppression of EAMG is accompanied by down-regulation of the costimulatory factor CD40L and up-regulation of CTLA-4, a key negative immunomodulator [8].
• Systemic short-term administration of 400 microg total of an anti-CD28 monoclonal antibody also prolonged corneal graft survival significantly (P < 0.05) and was more effective than systemic administration of 2 mg total of CTLA4-fusion protein (P < 0.05) [9].

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].

References