Guo J, Stolina M, Bready J V, Yin S, Horan T, Yoshinaga S K, Senaldi G
Amgen Inc., Thousand Oaks, CA 91320, USA.
J Immunol. 2001 May 1;166(9):5578-84. doi: 10.4049/jimmunol.166.9.5578.
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 humoral immune responses were investigated giving mice a construct with the extracellular domain of murine B7RP-1 fused with human IgG1 Fc (B7RP-1-Fc). B7RP-1-Fc stimulated contact hypersensitivity (CH) given near either the time of sensitization or challenge 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 induce CH when transfused into naive mice. B7RP-1-Fc stimulated the production of anti-keyhole limpet hemocyanin (KLH) Ab, increasing anti-KLH IgG, IgG2a, 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 with KLH and their production of IFN-gamma, IL-4, and IL-10 in response to KLH. Finally, B7RP-1-Fc increased the presence of eosinophils in the bronchoalveolar lavage and lungs of mice sensitized and challenged with OVA so to mount an asthmatic reaction. B7RP-1-Fc stimulates both cellular and humoral immune responses in vivo by increasing number and function of T and B cells reacting to Ag exposure.
诱导性共刺激分子（ICOS）和B7相关蛋白-1（B7RP-1）构成参与T细胞共刺激的受体-配体对。在本研究中，通过给小鼠注射含鼠源B7RP-1胞外结构域与人IgG1 Fc融合的构建体（B7RP-1-Fc），研究了B7RP-1对细胞免疫和体液免疫反应的刺激作用。在致敏或用恶唑酮激发时给予B7RP-1-Fc可刺激接触性超敏反应（CH）。在激发时给予B7RP-1-Fc比给予含鼠源B7.2胞外结构域和Fc的构建体（B7.2-Fc）更能刺激CH。B7RP-1-Fc增加了恶唑酮致敏皮肤引流淋巴结中的细胞数量，尤其是活化的T细胞。当将这些淋巴结中的细胞输注到未致敏小鼠中时，B7RP-1-Fc也增强了这些细胞诱导CH的能力。B7RP-1-Fc刺激抗钥孔血蓝蛋白（KLH）抗体的产生，增加抗KLH IgG、IgG2a和IgE，而B7.2-Fc不影响这种产生。B7RP-1-Fc还增加了用KLH免疫皮肤引流淋巴结中的细胞数量及其对KLH反应产生的干扰素-γ、白细胞介素-4和白细胞介素-10。最后，B7RP-1-Fc增加了用卵清蛋白致敏和激发以引发哮喘反应的小鼠支气管肺泡灌洗和肺中嗜酸性粒细胞的数量。B7RP-1-Fc通过增加对抗原暴露作出反应的T和B细胞的数量和功能来刺激体内的细胞免疫和体液免疫反应。
