Ramirez F, McKnight A J, Silva A, Mason D
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
J Exp Med. 1992 Dec 1;176(6):1551-9. doi: 10.1084/jem.176.6.1551.
Rat T lymphocytes, activated in vitro with concanavalin A (Con A), were shown by flow cytofluorographic analysis to contain a population of cells that simultaneously expressed CD4 and the alpha chain of CD8. The inclusion of the glucocorticoid hormone dexamethasone in the culture medium greatly increased both the frequency of these double-positive cells and the level of CD8 alpha chain expression. The level of expression of CD4 was not affected, and the cells that expressed CD8 antigen only also remained unchanged in surface phenotype. Detailed studies demonstrated unequivocally that the CD4+ CD8 alpha + cells were not artifacts produced by the random association of single-positive cells in the flow cytofluorograph, but arose from precursors that were single-positive CD4+ cells before activation. Furthermore, Con A activation of purified CD4+ T cells, in the presence of T cell-depleted accessory cells, showed that CD8+ T cells played no role in the induction process. However, the induction of CD8 alpha chain expression on CD4+ T cells and the enhancement of this expression by dexamethasone were almost completely inhibited by rat recombinant interleukin 4 (IL-4). Detection of mRNA for rat CD8 alpha chain by Northern blot closely paralleled the cell surface expression of CD8 alpha antigen, indicating that dexamethasone and IL-4 had opposing effects on mRNA levels. In contrast, IL-4 and dexamethasone both induced CD8 alpha chain expression on a rat CD4+ T cell clone when this was activated by specific antigen, and, although the effect with IL-4 was relatively weak, it did not antagonize the effect of the glucocorticoid. The possible significance of these results is briefly discussed.
用伴刀豆球蛋白A（Con A）在体外激活的大鼠T淋巴细胞，经流式细胞荧光分析显示，其中一群细胞同时表达CD4和CD8的α链。在培养基中加入糖皮质激素地塞米松，可大大增加这些双阳性细胞的频率以及CD8α链的表达水平。CD4的表达水平不受影响，仅表达CD8抗原的细胞其表面表型也保持不变。详细研究明确表明，CD4+CD8α+细胞不是流式细胞荧光仪中单个阳性细胞随机结合产生的假象，而是由激活前为单阳性CD4+细胞的前体细胞产生的。此外，在去除T细胞的辅助细胞存在的情况下，用Con A激活纯化的CD4+T细胞，结果显示CD8+T细胞在诱导过程中不起作用。然而，大鼠重组白细胞介素4（IL-4）几乎完全抑制了CD4+T细胞上CD8α链表达的诱导以及地塞米松对该表达的增强作用。通过Northern印迹法检测大鼠CD8α链的mRNA，其结果与CD8α抗原的细胞表面表达密切平行，表明地塞米松和IL-4对mRNA水平具有相反的作用。相比之下，当大鼠CD4+T细胞克隆被特异性抗原激活时，IL-4和地塞米松均可诱导其CD8α链表达，并且尽管IL-4的作用相对较弱，但它并不拮抗糖皮质激素的作用。本文简要讨论了这些结果可能的意义。
