Akiba H, Oshima H, Takeda K, Atsuta M, Nakano H, Nakajima A, Nohara C, Yagita H, Okumura K
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
J Immunol. 1999 Jun 15;162(12):7058-66.
OX40 and its ligand (OX40L) have been implicated in T cell-dependent humoral immune responses. To further characterize the role of OX40/OX40L in T-B cell interaction, we newly generated an anti-mouse OX40L mAb (RM134L) that can inhibit the costimulatory activity of OX40L transfectants for anti-CD3-stimulated T cell proliferation. Flow cytometric analyses using RM134L and an anti-mouse OX40 mAb indicated that OX40 was inducible on splenic T cells by stimulation with immobilized anti-CD3 mAb in a CD28-independent manner, while OX40L was not expressed on resting or activated T cells. OX40L was inducible on splenic B cells by stimulation with anti-IgM Ab plus anti-CD40 mAb, but not by either alone. These activated B cells exhibited a potent costimulatory activity for anti-CD3-stimulated T cell proliferation and IL-2 production. Anti-CD80 and anti-CD86 mAbs partially inhibited the costimulatory activity, and further inhibition was obtained by their combination with RM134L and/or anti-CD70 mAb. We also found the anti-IgM Ab- plus anti-CD40 mAb-stimulated B cells exhibited a potent costimulatory activity for proliferation of and IL-2 production by anti-CD3-stimulated CD28- T cells from CD28-deficient mice, which was substantially inhibited by RM134L and/or anti-CD70 mAb. These results indicated that OX40L and CD70 expressed on surface Ig- and CD40-stimulated B cells can provide CD28-independent costimulatory signals to T cells.
OX40及其配体（OX40L）已被证明参与T细胞依赖性体液免疫反应。为了进一步阐明OX40/OX40L在T-B细胞相互作用中的作用，我们新制备了一种抗小鼠OX40L单克隆抗体（RM134L），该抗体可抑制OX40L转染细胞对抗CD3刺激的T细胞增殖的共刺激活性。使用RM134L和抗小鼠OX40单克隆抗体进行的流式细胞术分析表明，固定化抗CD3单克隆抗体刺激可使脾脏T细胞以不依赖CD28的方式诱导表达OX40，而静止或活化的T细胞不表达OX40L。抗IgM抗体加抗CD40单克隆抗体刺激可诱导脾脏B细胞表达OX40L，单独使用其中任何一种抗体则不能诱导。这些活化的B细胞对抗CD3刺激的T细胞增殖和IL-2产生具有强大的共刺激活性。抗CD80和抗CD86单克隆抗体可部分抑制共刺激活性，将它们与RM134L和/或抗CD70单克隆抗体联合使用可进一步增强抑制效果。我们还发现，抗IgM抗体加抗CD40单克隆抗体刺激的B细胞对CD28缺陷小鼠来源的抗CD3刺激的CD28-T细胞的增殖和IL-2产生具有强大的共刺激活性，RM134L和/或抗CD70单克隆抗体可显著抑制这种活性。这些结果表明，表面Ig和CD40刺激的B细胞上表达的OX40L和CD70可向T细胞提供不依赖CD28的共刺激信号。
