Human T helper cell differentiation is regulated by the combined action of cytokines and accessory cell-dependent costimulatory signals.
Human T helper cell differentiation is regulated by the combined action of cytokines and accessory cell-dependent costimulatory signals.
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DOI：
10.4049/jimmunol.158.6.2654
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发表时间：
1997-03
影响因子：
4.4
通讯作者：
E. M. Palmer;G. Seventer
中科院分区：
文献类型：
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作者：
E. M. Palmer;G. Seventer
我们已经开发了一个体外分化的人Th细胞模型，研究细胞因子和辅助细胞依赖的共刺激信号在这一过程中的作用。外周血来源的CD 4+“幼稚”（CD 45 RA + RO-）T细胞以每周的间隔用固定化抗CD 3 mAb、辅助细胞和外源性细胞因子刺激，并分析细胞因子分泌模式。以B细胞系JY（B7-1+ B7-2+）为辅助细胞来源，可产生不同的Th细胞亚群。与重组人（rh）IL-1 β和rhIL-6的组合共培养产生Th 0样细胞，其分泌低水平的IFN-γ和IL-5。rhIL-12的添加导致Th 1样细胞的产生，其分泌高水平的IL-2、IFN-γ、TNF-α，并且在多次刺激下，分泌显著水平的IL-10。rhIL-4的存在诱导Th 2样细胞分泌高水平的IL-5和IL-13，但检测不到IL-4水平。只有在用佛波酯和钙离子载体刺激后，这些Th 2样细胞才能被诱导分泌显著水平的IL-4，表明与IL-4相比，诱导IL-5和IL-13具有不同的刺激需求。B7-1阴性的单核细胞系U937只能为Th 1样细胞的产生提供辅助细胞依赖的共刺激信号，而B7-1转染的U937细胞获得了为Th 2样细胞的产生提供共刺激的能力。这些结果表明，CD 28介导的共刺激的差异依赖于人类Th 1样和Th 2样细胞的产生。
We have developed an in vitro differentiation model for human Th cells to study the role of cytokines and accessory cell-dependent costimulatory signals in this process. Peripheral blood-derived CD4+ "naive" (CD45RA+ RO-) T cells were stimulated in weekly intervals with immobilized anti-CD3 mAb, accessory cells, and exogenous cytokines, and were analyzed for cytokine secretion pattern. With the B cell line JY (B7-1+ B7-2+), as source of accessory cells, we could generate distinct Th subsets. Coculture with the combination of recombinant human (rh) IL-1beta and rhIL-6 gave rise to Th0-like cells, which secreted low levels of IFN-gamma and IL-5. The addition of rhIL-12 led to the generation of Th1-like cells, which secreted high levels of IL-2, IFN-gamma, TNF-alpha, and upon multiple stimulations, significant levels of IL-10. The presence of rhIL-4 induced Th2-like cells that secreted high levels of IL-5 and IL-13, but undetectable levels of IL-4. Only after stimulation with phorbol ester and calcium ionophore could these Th2-like cells be induced to secrete significant levels of IL-4, indicating distinct stimulatory requirements for the induction of IL-5 and IL-13 compared with IL-4. The B7-1-negative monocytic cell line U937 could only provide accessory cell-dependent costimulatory signals for the generation of Th1-like cells, while B7-1-transfected U937 cells acquired the capacity to provide costimulation for the generation of Th2-like cells. These results indicate a differential dependence on CD28-mediated costimulation for the generation of human Th1-like and Th2-like cells.