Antigen-stimulated CD4 T-cell expansion is inversely and log-linearly related to precursor number
Antigen-stimulated CD4 T-cell expansion is inversely and log-linearly related to precursor number
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DOI：
10.1073/pnas.1018525108
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发表时间：
2011-02-22
影响因子：
11.1
通讯作者：
Paul，William E.
中科院分区：
文献类型：
--
作者：
Quiel，Juan;Caucheteux，Stephane;Paul，William E.
随着输注细胞数量的增加，抗原驱动的特定CD4T细胞的扩增在每个细胞的基础上减少。对数前兆数与对数膨胀因子(FE)呈线性关系，在3~30,000个前兆范围内，∼−斜率为0.5。在较低的前体细胞数下观察到FE的细胞数量依赖性，这意味着潜在的过程在生理上调节抗原驱动的T细胞增殖。少量转基因前体的FE不受大量细胞对不同抗原的伴随反应的显著影响。增加抗原量或外源性IL-2、IL-7或IL-15对FE无显著影响，FE也不依赖于Fas、肿瘤坏死因子-α受体、细胞毒性T淋巴细胞抗原-4、IL-2或干扰素-γ。少量缺失Foxp3的T细胞受体转基因细胞比大量转基因细胞扩增幅度更大，这意味着这种效应不是由调节性T细胞介导的。增加树突状细胞数量确实会导致更大的FE，但FE与前体数量之间的定量关系并未被废除。虽然不排除多肽/MHC复合体的竞争作为解释，但随着前体数量的增加，FE的下降可以用负反馈来解释，即一个簇中反应细胞的数量增加抑制了该簇内相同特异性细胞的扩张。
Antigen-driven expansion of specific CD4 T cells diminishes, on a per cell basis, as infused cell number increases. There is a linear relation between log precursor number and log factor of expansion (FE), with a slope of ∼−0.5 over a range from 3 to 30,000 precursors. Cell number dependence of FE is observed at low precursor number, implying that the underlying process physiologically regulates antigen-driven T-cell expansion. FE of small numbers of transgenic precursors is not significantly affected by concomitant responses of large numbers of cells specific for different antigens. Increasing antigen amount or exogenous IL-2, IL-7, or IL-15 does not significantly affect FE, nor does FE depend on Fas, TNF-α receptor, cytotoxic T-lymphocyte antigen-4, IL-2, or IFN-γ. Small numbers of Foxp3-deficient T-cell receptor transgenic cells expand to a greater extent than do large numbers, implying that this effect is not mediated by regulatory T cells. Increasing dendritic cell number does result in larger FE, but the quantitative relation between FE and precursor number is not abrogated. Although not excluding competition for peptide/MHC complexes as an explanation, fall in FE with increasing precursor number could be explained by a negative feedback in which increasing numbers of responding cells in a cluster inhibit the expansion of cells of the same specificity within that cluster.