Blocking T cell co-stimulation using a CD80 blocking small molecule reduces delayed type hypersensitivity responses in rhesus monkeys.
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, 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 inhibited proinflammatory cytokine release and cellular proliferation with micromolar potency. Systemic administration of RhuDex 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.
Haanstra
K G
KG
Biomedical Primate Research Centre, Rijswijk, the Netherlands. haanstra@bprc.nl
Endell
J
J
Estévâo
D
D
Kondova
I
I
Jonker
M
M
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000628:therapy*; D007371:Interferon-gamma / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects; D008253:Macaca mulatta; D023421:Models, Animal; D010047:Ovalbumin; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013745:Tetanus Toxoid
D018122:B7-1 Antigen; D013745:Tetanus Toxoid; D007371:Interferon-gamma; D010047:Ovalbumin