Blocking T cell co-stimulation using a CD80 blocking small molecule reduces delayed type hypersensitivity responses in rhesus monkeys

• Published in: Clinical and experimental immunology Vol. 158; no. 1; pp. 91 - 98
• Main Authors: Haanstra, K.G, Endell, J, Estévâo, D, Kondova, I, Jonker, M
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.10.2009; Blackwell Publishing Ltd; Blackwell; Blackwell Science Inc
• Subjects: Allergic diseases; Analytical, structural and metabolic biochemistry; Animals; Antigen-Presenting Cells - drug effects; Antigen-Presenting Cells - immunology; B7-1 Antigen - immunology; Biological and medical sciences; Cell Line; Cell Proliferation - drug effects; Cells, Cultured; co-stimulation; DTH; Fundamental and applied biological sciences. Psychology; Hypersensitivity, Delayed - immunology; Hypersensitivity, Delayed - therapy; Immunopathology; Interferon-gamma - analysis; Lymphocyte Activation - drug effects; Macaca mulatta; Medical sciences; Models, Animal; non-human primate; Ovalbumin; Skin - immunology; Skin allergic diseases. Stinging insect allergies; small molecule; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tetanus Toxoid; Translational Studies; Allergy; Immunopathology; small molecule; Nonhuman primate; Monkey; Blocking; Biochemistry; Delayed hypersensitivity; Macaca mulatta; Costimulatory molecule; co-stimulation; Vertebrata; Delayed response; Mammalia; non-human primate; B7-1 Molecule; Costimulation; T-Lymphocyte; Primates; Simioidea; DTH
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2009.03994.x

Blockade of co-stimulation signals between T cells and antigen-presenting cells could be an important approach for treatment of autoimmune diseases and transplant rejection. Recently a series of small compound inhibitors which bind human CD80 (B7-1) and inhibit T cell co-stimulation has been described. To investigate their potency for clinical use, one of these compounds, RhuDex[trade mark sign], was evaluated for reactivity with rhesus monkey CD80. The in vitro biological effect on rhesus monkey lymphocytes, the potency for suppression of an inflammatory recall response and the protein-induced delayed type hypersensitivity (DTH) response in the skin were studied. In a rhesus monkey T cell co-stimulation assay RhuDex[trade mark sign] inhibited proinflammatory cytokine release and cellular proliferation with micromolar potency. Systemic administration of RhuDex[trade mark sign] to rhesus monkeys inhibited the DTH response significantly, indicating that this compound may inhibit autoimmune mediated inflammatory processes where the target, CD80, is up-regulated.