Swain S L, Weinberg A D, English M
Department of Biology, University of California, San Diego 92093.
J Immunol. 1990 Mar 1;144(5):1788-99.
We have studied the properties of several developmentally defined subpopulations of CD4+ T cells from normal animals which can be stimulated to secrete lymphokines. We find that the Th cells responsible for direct secretion of lymphokines after stimulation are from a resting, very long lived subpopulation of CD4+ T cells which persists for over 25 wk after adult thymectomy. These T cells are depleted by in vivo administration of antithymocyte serum and they are enriched among T cells which express high levels of Pgp-1. This phenotype suggests that the T cells responsible are most likely memory T cells which have resulted from antigen exposure in vivo. T cells in this subset secrete predominantly IL-2 with small quantities of IL-3, granulocyte/macrophage CSF, and IFN-gamma. In contrast, the CD4+ T cells which require in vitro culture and restimulation before they develop into an effector population with the ability to secrete lymphokines after restimulation, differ dramatically by most of these criteria. The precursors we study are resting Th cells which are considerably shorter lived after adult thymectomy (5 to 10 wk) and resistant to the same doses of antithymocyte serum which deplete the putative memory population. We hypothesize that this precursor population represents naive helper cells which have not yet encountered Ag. The effectors derived from such precursors can be stimulated to secrete high levels of both Th cell types 1 and 2 lymphokines (IFN-gamma, IL-4, IL-5, granulocyte/macrophage CSF, and IL-3). Generation of effectors requires proliferation and differentiation events which occur during a mandatory culture with lymphokines and antigen presenting cells for 3 to 4 days. We discuss the striking phenotypic and functional differences among these subpopulations of helper cells--the precursor population and the two types--memory and cultured effector Th which secrete lymphokines. We also discuss the relationship of these populations to CD4+ T cell subsets defined by other studies of patterns of lymphokine secretion and by cell surface phenotype.
我们研究了来自正常动物的几个发育定义的CD4 + T细胞亚群的特性，这些亚群可被刺激分泌淋巴因子。我们发现，刺激后负责直接分泌淋巴因子的Th细胞来自CD4 + T细胞的静止、寿命极长的亚群，成年胸腺切除术后该亚群持续存在超过25周。这些T细胞通过体内给予抗胸腺细胞血清而减少，并且在表达高水平Pgp-1的T细胞中富集。这种表型表明，负责的T细胞很可能是体内抗原暴露产生的记忆T细胞。该亚群中的T细胞主要分泌IL-2，少量分泌IL-3、粒细胞/巨噬细胞集落刺激因子和IFN-γ。相比之下，需要体外培养和再刺激才能发育成再刺激后能够分泌淋巴因子的效应细胞群的CD4 + T细胞，在大多数这些标准上有显著差异。我们研究的前体是静止的Th细胞，成年胸腺切除术后寿命相当短（5至10周），并且对耗尽假定记忆群体的相同剂量的抗胸腺细胞血清具有抗性。我们假设这个前体群体代表尚未遇到抗原的幼稚辅助细胞。源自此类前体的效应细胞可被刺激分泌高水平的Th1和Th2型淋巴因子（IFN-γ、IL-4、IL-5、粒细胞/巨噬细胞集落刺激因子和IL-3）。效应细胞的产生需要在与淋巴因子和抗原呈递细胞进行3至4天的强制培养期间发生增殖和分化事件。我们讨论了这些辅助细胞亚群——前体群体以及分泌淋巴因子的记忆和培养效应Th这两种类型——之间显著的表型和功能差异。我们还讨论了这些群体与通过其他淋巴因子分泌模式研究和细胞表面表型定义的CD4 + T细胞亚群的关系。
