Role of monocytes in anti-CD3-induced T-cell DNA synthesis: effect of chloroquine and monensin on anti-CD3-induced human T-cell activation.
Role of monocytes in anti-CD3-induced T-cell DNA synthesis: effect of chloroquine and monensin on anti-CD3-induced human T-cell activation.
复制标题
单核细胞在抗 CD3 诱导的 T 细胞 DNA 合成中的作用：氯喹和莫能菌素对抗 CD3 诱导的人 T 细胞活化的影响。
DOI：
10.1007/bf00916700
复制
发表时间：
1990
影响因子：
9.1
通讯作者：
Gupta,S
中科院分区：
文献类型：
--
作者：
Vayuvegula,B;Ohira,K;Gollapudi,S;Gupta,S
抗CD3单抗仅在单核/巨噬细胞存在的情况下才能诱导新鲜分离的外周血T细胞增殖，并且需要抗体的Fc部分与单核/巨噬细胞结合。在这项研究中，我们研究了单核细胞是否处理与任何可溶性抗原相似的抗CD3抗体，并呈现给与人类白细胞抗原DR相关的T细胞，以诱导最大的DNA合成。用抗CD3单抗冲击贴壁的单核细胞，在存在或不存在抑制可溶性抗原加工的溶致变色剂氯喹和莫能菌素的情况下，广泛洗涤，然后在没有可溶性抗CD3的情况下与自体T细胞孵育，测定~3H-胸腺嘧啶核苷掺入和CD25表达。莫能菌素和氯喹均以剂量依赖方式抑制抗CD3冲击的单核细胞诱导的T细胞DNA合成和CD25表达。这种抑制作用不是由于细胞活力的丧失或对单核细胞表面人类白细胞抗原-DR表达的影响。经抗CD3单抗冲击的多聚甲醛固定的单核细胞在自体T细胞上诱导的DNA合成、HLA-DR表达和CD25抗原表达明显低于未冲击抗CD3的单核细胞。抗CD3冲击的单核细胞与框架特异性的抗人类白细胞抗原-DR单抗一起处理，抑制了它们诱导T细胞DNA合成的能力。这些数据表明，单核细胞除了作为交联的基质外，还处理抗CD3单抗，并在人类白细胞抗原-DR的背景下呈递给T细胞，以诱导最佳的DNA合成。
Anti-CD3 monoclonal antibody (MoAb) induces proliferation of freshly isolated peripheral blood T cells only in the presence of monocytes/macrophages and requires binding of the Fc portion of antibody to monocytes/macrophages. In this investigation, we examined whether monocytes process anti-CD3 similar to any soluble antigen and present to T cells in context with HLA-DR to induce maximal DNA synthesis. Adherent monocytes were pulsed with anti-CD3 MoAb in the presence or absence of the lysozomotropic agents chloroquine and monensin, which are known to inhibit processing of soluble antigens, washed extensively, and then incubated with autologous T cells in the absence of soluble anti-CD3, and3H-thymidine incorporation and CD25 expression were measured. Both monensin and chloroquine inhibited anti-CD3-pulsed monocyte-induced T-cell DNA synthesis and CD25 expression in a dose-dependent manner. This inhibitory effect was not due to any loss in cell viability or the effect on the expression of HLA-DR on monocytes. Paraformaldehyde-fixed monocytes pulsed with anti-CD3 MoAb induced significantly less DNA synthesis, HLA-DR expression, and CD25 antigen expression on autologous T cells as compared to responses induced by unfixed anti-CD3-pulsed monocytes. The treatment of anti-CD3-pulsed monocytes with frame-work-specific anti-HLA-DR MoAb inhibited their capacity to induce T-cell DNA synthesis. These data suggest that monocytes, in addition to serving as the matrix for cross-linking, also process anti-CD3 MoAb and present to the T cells in the context of HLA-DR antigens to induce optimal DNA synthesis.