de Jong R, Brouwer M, Kuiper H M, Hooibrink B, Miedema F, van Lier R A
Department of Clinical Viro-Immunology, The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
J Immunol. 1992 Oct 15;149(8):2795-802.
The human CD45R0+ (memory) CD4+ T cell population can be subdivided into a large (82%) CD27+ and a small (18%) CD27- subset. Within the CD45R0+CD27- subset, cells accumulate that have been persistently stimulated by Ag in vivo. As an apparent consequence, TLC with a differentiated functional phenotype, producing either high levels of IFN-gamma (Th1-like), high levels of IL-4 (Th2-like) or high amounts of both these cytokines (here referred to as Thx) can primarily be generated from the CD27- memory CD4+ T cell subset. In this study we examined the requirements for induction of proliferation of distinct CD4+CD45R0+ Th subsets. Immobilized CD3 mAb induced proliferation with comparable magnitude and kinetics in all types of TLC. However, interference with intracellular signaling pathways in this activation system, resulted in a strong inhibition of proliferation in TLC derived from CD27+ cells whereas, in contrast, TLC from CD27- cells were relatively resistant to elevation of [cAMP]i, inhibition of protein kinase C activation and the immunosuppressive effects of cyclosporin A. Stimulation with CD3 mAb in soluble form resulted in Il-4 secretion by Th2-like and Thx-type TLC but did not induce IFN-gamma or Il-2 secretion in any Th subset. Interestingly, Th2-like cells but not Thx-type cells were able to use endogenously produced Il-4 for proliferation. These data demonstrate a differential sensitivity of CD45R0+CD4+ Th subsets for immune activation and suppression, which correlated with their maturation stage, as reflected by CD27 membrane expression, as well as with their effector phenotype.
人类CD45R0 +（记忆性）CD4 + T细胞群体可细分为一个较大的（82%）CD27 +亚群和一个较小的（18%）CD27 -亚群。在CD45R0 + CD27 -亚群中，积累了在体内被抗原持续刺激的细胞。显然，结果是，具有分化功能表型、产生高水平干扰素-γ（Th1样）、高水平白细胞介素-4（Th2样）或这两种细胞因子都大量产生（这里称为Thx）的TLC主要可从CD27 -记忆性CD4 + T细胞亚群中产生。在本研究中，我们研究了诱导不同CD4 + CD45R0 + Th亚群增殖的条件。固定化的CD3单克隆抗体在所有类型的TLC中诱导出具有相当幅度和动力学的增殖。然而，在这个激活系统中干扰细胞内信号通路，导致源自CD27 +细胞的TLC增殖受到强烈抑制，而相比之下，来自CD27 -细胞的TLC对细胞内[环磷酸腺苷]升高、蛋白激酶C激活的抑制以及环孢素A的免疫抑制作用相对具有抗性。用可溶性形式的CD3单克隆抗体刺激导致Th2样和Thx型TLC分泌白细胞介素-4，但在任何Th亚群中都不诱导干扰素-γ或白细胞介素-2分泌。有趣的是，Th2样细胞而不是Thx型细胞能够利用内源性产生的白细胞介素-4进行增殖。这些数据表明CD45R0 + CD4 + Th亚群对免疫激活和抑制具有不同的敏感性，这与其成熟阶段相关，如通过CD27膜表达所反映的，也与其效应器表型相关。
