Stimulatory effects of B7-related protein-1 on cellular and humoral immuneresponses in mice

Inducible costimulator (ICOS) and B7-related protein-1 (B7RP-1) constitute a receptor-ligand pair involved in T cell costimulation. In this study, the stimulatory effects of B7RP-1 on cellular and Immoral immune responses wer e investigated giving mice a construct with the extracellular domain of mur ine B7RP-1 fused with human IgG1 Fe (B7RP-1-Fc). B7RP-1-Fc stimulated conta ct hypersensitivity (CH) given near either the time of sensitization or cha llenge with oxazolone. When given near challenge time, B7RP-1-Fc stimulated CH more than a construct containing the extracellular domain of murine B7. 2 and Fc (B7.2-Fc). B7RP-1-Fc increased the number of cells in lymph nodes draining the skin sensitized with oxazolone, especially activated T cells. B7RP-1-Fc also increased the ability of the cells in these lymph nodes to i nduce CH when transfused into naive mice. B7RP-1-Fc stimulated the producti on of anti-keyhole limpet hemocyanin (KLH) Ab, increasing anti-KLH IgG, IgG 2a, and IgE, whereas B7.2-Fc did not affect this production. B7RP-1-Fc also increased the number of cells in lymph nodes draining the skin immunized w ith KLH and their production of IFN-gamma, IL-4, and IL-10 in response to K LH. Finally, B7RP-1-Fc increased the presence of eosinophils in the broncho alveolar lavage and lungs of mice sensitized and challenged with OVA so to mount an asthmatic reaction. B7RP-1-Fc stimulates both cellular and Immoral immune responses in vivo by increasing number and function of T and B cell s reacting to Ag exposure.