Williams J M, Deloria D, Hansen J A, Dinarello C A, Loertscher R, Shapiro H M, Strom T B
J Immunol. 1985 Oct;135(4):2249-55.
A mitogenic anti-CD3 ("T3") monoclonal antibody (64.1), that stimulates polyclonal T cell activation by a mechanism believed to be similar to antigen via binding to the T cell receptor complex, was utilized in soluble (SOL) and Sepharose-bound (SEPH) forms to dissect the role of accessory cells (AC) and interleukin 1 (IL 1) in supporting T cell activation. The T cell activation pathway was dissected into "early" events including expression of interleukin 2 receptors (IL 2R), increased RNA content, IL 2 release, and "late" (DNA synthesis) events. Unseparated peripheral blood mononuclear cells progressed through all stages of activation when stimulated by either form of 64.1. Stringent AC depletion by plastic adherence, nylon wool adherence, and L-leucine methyl ester (selectively lyses AC) prevented early and late T cell responses to either form of 64.1. The addition of highly purified IL 1 replenished both early and late T cell responses to SEPH-64.1 but not to SOL-64.1. Although SOL-64.1 stimulation of purified T cells induced modulation of the CD3 complex, only SEPH-64.1 induced IL 1 responsiveness, and exogenous IL 1 was then able to support synthesis of RNA, secretion of IL 2, expression of IL 2R, and ultimately, DNA synthesis. Therefore, the stages of early T cell activation owing to stimulation of the CD3-T cell receptor complex and IL 1 responsiveness have been dissected.
一种促有丝分裂抗CD3（“T3”）单克隆抗体（64.1），其通过一种被认为类似于抗原与T细胞受体复合物结合的机制刺激多克隆T细胞活化，以可溶性（SOL）和琼脂糖结合（SEPH）形式用于剖析辅助细胞（AC）和白细胞介素1（IL 1）在支持T细胞活化中的作用。T细胞活化途径被分为“早期”事件，包括白细胞介素2受体（IL 2R）的表达、RNA含量增加、IL 2释放，以及“晚期”（DNA合成）事件。当受到任何一种形式的64.1刺激时，未分离的外周血单核细胞会经历活化的所有阶段。通过塑料黏附、尼龙毛黏附和L - 亮氨酸甲酯（选择性裂解AC）进行严格的AC耗竭可阻止T细胞对任何一种形式的64.1产生早期和晚期反应。添加高度纯化的IL 1可恢复T细胞对SEPH - 64.1的早期和晚期反应，但不能恢复对SOL - 64.1的反应。尽管SOL - 64.1刺激纯化的T细胞可诱导CD3复合物的调节，但只有SEPH - 64.1可诱导IL 1反应性，然后外源性IL 1能够支持RNA合成、IL 2分泌、IL 2R表达，并最终支持DNA合成。因此，已剖析了由于CD3 - T细胞受体复合物刺激和IL 1反应性导致的早期T细胞活化阶段。
