Armant M, Rubio M, Delespesse G, Sarfati M
University of Montreal, Louis-Charles Simard Research Center, Quebec, Canada.
J Immunol. 1995 Nov 15;155(10):4868-75.
The majority of T cells at the site of an inflammatory lesion do not appear to be Ag-specific, but they still contribute to the inflammatory response. Herein, we report that sCD23 activates monocytes to participate in the stimulation of resting T cells in the absence of TCR engagement. First, sCD23 selectively triggers monokine release by purified monocytes in the absence of costimulus. It induces TNF-alpha, IL-1 beta, IL-8, granulocyte-macrophage-CSF, and prostaglandin E2 but no IL-10, IL-12, TGF-beta, or leukotriene B4. The sCD23-induced TNF-alpha production is significantly inhibited by IL-4 and IL-10 but not by TGF-beta. Also, monocytes activated by sCD23 express decreased levels of HLA-DR and increased levels of CD14, CD54, CD40, and B7 Ag. Next, we show that, in the presence of monocytes, sCD23 is a potent costimulator of IL-2 or IL-12-induced IFN-gamma production by resting T cells in the absence of exogenous Ag and that this effect is partially reduced by anti-TNF-alpha mAb. B cells cannot substitute for monocytes, and CD4+ and CD8+ T cells are equal responders. The data further indicate that monocyte-T cell contact, more particularly CD40-CD40L interactions, is required for IFN-gamma production in response to IL-2 plus sCD23, and the response to IL-12 plus sCD23 is CD40- and B7-independent but is still partially contact-dependent. It is proposed that sCD23, when produced locally at a site of immune response, may trigger an inflammatory process via monokine release and may further amplify it via the stimulation of bystander non-Ag-specific T cells.
炎症损伤部位的大多数T细胞似乎并非抗原特异性的，但它们仍参与炎症反应。在此，我们报告可溶性CD23（sCD23）可激活单核细胞，使其在没有T细胞受体（TCR）参与的情况下参与对静息T细胞的刺激。首先，sCD23在无共刺激的情况下选择性地触发纯化单核细胞释放单核因子。它可诱导肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-8（IL-8）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和前列腺素E2，但不诱导IL-10、IL-12、转化生长因子-β（TGF-β）或白三烯B4。sCD23诱导的TNF-α产生受到IL-4和IL-10的显著抑制，但不受TGF-β的抑制。此外，被sCD23激活的单核细胞表达水平降低的人类白细胞抗原-DR（HLA-DR）以及水平升高的CD14、CD54、CD40和B7抗原。接下来，我们表明，在存在单核细胞的情况下，sCD23是静息T细胞在无外源性抗原时由IL-2或IL-12诱导产生干扰素-γ（IFN-γ）的有效共刺激因子，并且这种效应被抗TNF-α单克隆抗体部分减弱。B细胞不能替代单核细胞，并且CD4⁺和CD8⁺ T细胞是同等反应者。数据进一步表明，单核细胞-T细胞接触，尤其是CD40-CD40L相互作用，是对IL-2加sCD23产生IFN-γ所必需的，并且对IL-12加sCD23的反应不依赖CD40和B7，但仍部分依赖细胞接触。有人提出，sCD23在免疫反应部位局部产生时，可能通过单核因子释放触发炎症过程，并可能通过刺激旁观者非抗原特异性T细胞进一步放大炎症反应。
