Arad G, Ketzinel M, Tal C, Nussinovich R, Deutsch E, Schlesinger M, Gerez L, Kaempfer R
Department of Molecular Virology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Cell Immunol. 1995 Feb;160(2):240-7. doi: 10.1016/0008-8749(95)80034-g.
The level of transient expression of human IL-2 and IFN-gamma genes, we show, is regulated by dynamic interaction between two functionally distinct cell populations. One is able to express these genes, while the other, bearing one of several specific surface markers, actively inhibits their expression. Defined cell subsets were isolated from PBMC and tonsil cells using immunomagnetic beads coated with monoclonal antibodies directed against surface markers. Depletion of CD8, CD11a (Leu15), or Leu8 subsets led to a pronounced superinduction of IL-2 and IFN-gamma gene expression when the remaining cell population was stimulated with mitogen (PHA) or antigen (SEB). Thus, a 10-fold increase in production of IFN-gamma was observed after removal of CD11a (Leu15) cells constituting only a small percentage of the total cell population. By contrast, depletion of cells expressing CD19, a B cell marker, did not yield any superinduction. Conversely, CD8, CD11a (Leu15), or Leu8 cell subsets, but not CD19 cells, each inhibited the induction of IL-2 and IFN-gamma gene expression almost completely in depleted or total cell populations from which they were derived. Gene expression occurring within one cell subset could be effectively inhibited by cells from a second subset. Introduction of inhibitory cells (Leu8) into a population that actively expressed IL-2 and IFN-gamma mRNA resulted in an immediate cessation of gene expression. This suppression involves a soluble mediator, since the culture medium in which such cells were activated exerted a similarly effective inhibition.
我们发现，人白细胞介素-2（IL-2）和干扰素-γ（IFN-γ）基因的瞬时表达水平受两种功能不同的细胞群体之间动态相互作用的调节。其中一种能够表达这些基因，而另一种带有几种特定表面标志物之一，可积极抑制它们的表达。使用包被有针对表面标志物的单克隆抗体的免疫磁珠，从外周血单核细胞（PBMC）和扁桃体细胞中分离出特定的细胞亚群。当用丝裂原（PHA）或抗原（SEB）刺激剩余细胞群体时，去除CD8、CD11a（Leu15）或Leu8亚群会导致IL-2和IFN-γ基因表达明显超诱导。因此，在去除仅占总细胞群体一小部分的CD11a（Leu15）细胞后，观察到IFN-γ产量增加了10倍。相比之下，去除表达B细胞标志物CD19的细胞并未产生任何超诱导现象。相反，CD8、CD11a（Leu15）或Leu8细胞亚群，而非CD19细胞，几乎完全抑制了来自它们所源自的耗尽或总细胞群体中IL-2和IFN-γ基因表达的诱导。一个细胞亚群内发生的基因表达可被第二个亚群的细胞有效抑制。将抑制性细胞（Leu8）引入积极表达IL-2和IFN-γ mRNA的群体中会导致基因表达立即停止。这种抑制涉及一种可溶性介质，因为激活这些细胞的培养基也发挥了类似的有效抑制作用。
