Buysmann S, Schellekens P T, Tax W J, ten Berge I J
Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
J Lab Clin Med. 1997 Jul;130(1):91-101. doi: 10.1016/s0022-2143(97)90063-9.
Murine CD3/T cell receptor (TCR) monoclonal antibodies (mAbs) induce immediate peripheral lymphocytopenias of different degree and duration. Lymphocytopenia is of short duration after the administration of immunoglobulin A CD3 mAb, but it persists much longer after the administration of immunoglobulin G2a CD3 mAb. Peripheral lymphocytopenia after the administration of WT31, a murine immunoglobulin G1 TCR mAb, appears to be dependent on the polymorphism of Fc(gamma)RIIa. In high responders, lymphocytopenia is comparable to that observed after immunoglobulin G2a CD3 mAb; in low responders, no lymphocytopenia occurs. In vitro, both immunoglobulin A and immunoglobulin G2a CD3 mAbs induce immediate activation of CD11a/CD18, with concomitant up-regulation of CD11b/CD18 on T cells, each of which is shown to be involved in the concurrent adhesion of T cells to endothelium. WT31 induces an immediate activation of CD11a/CD18 as well as T cell adhesion to endothelium in Fc(gamma)RIIa high responders only, interestingly without changes in the level of expression of CD11b/CD18. We conclude that the immediate occurrence of peripheral lymphocytopenia after the administration of CD3/TCR mAb is mediated by changes in the level of expression or avidity (or both) of adhesion molecules on T cells, whereas the persistence of this lymphocytopenia depends on the isotype of the CD3/TCR mAb and on the presence of suitable Fc receptors.
小鼠CD3/T细胞受体(TCR)单克隆抗体(mAb)可诱导不同程度和持续时间的即刻外周淋巴细胞减少。给予免疫球蛋白A CD3 mAb后淋巴细胞减少持续时间较短,但给予免疫球蛋白G2a CD3 mAb后持续时间长得多。给予小鼠免疫球蛋白G1 TCR mAb WT31后的外周淋巴细胞减少似乎取决于Fc(γ)RIIa的多态性。在高反应者中,淋巴细胞减少与给予免疫球蛋白G2a CD3 mAb后观察到的情况相当;在低反应者中,不发生淋巴细胞减少。在体外,免疫球蛋白A和免疫球蛋白G2a CD3 mAb均可诱导CD11a/CD18即刻激活,同时T细胞上的CD11b/CD18上调,其中每一种均显示参与T细胞与内皮细胞的同时黏附。WT31仅在Fc(γ)RIIa高反应者中诱导CD11a/CD18即刻激活以及T细胞与内皮细胞黏附,有趣的是CD11b/CD18的表达水平没有变化。我们得出结论,给予CD3/TCR mAb后外周淋巴细胞减少的即刻发生是由T细胞上黏附分子表达水平或亲和力(或两者)的变化介导的,而这种淋巴细胞减少的持续时间取决于CD3/TCR mAb的同种型以及合适Fc受体的存在。