Le P T, Vollger L W, Haynes B F, Singer K H
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
J Immunol. 1990 Jun 15;144(12):4541-7.
We have shown that human thymic epithelial (TE) cells produce IL-1 alpha, IL-1 beta, and TE cells bind to thymocytes by CD2 and LFA-1 molecules on thymocytes and LFA-3, ICAM-1 on TE cells. We investigated whether ligand binding to LFA-3 on human TE cells can modulate TE cell IL-1 production. First, we investigated the ability of human thymocytes to regulate IL-1 release by TE cells. Both autologous and allogenic emetine-treated thymocytes when cultured with TE cells augmented IL-1 release by TE cells. The augmentation of IL-1 release was cell density dependent. Inasmuch as the interaction between thymocytes and TE cells is mediated in part by CD2 molecules on thymocytes and LFA-3 molecules on TE cells we next determined the effect on IL-1 release of ligand binding (anti-LFA-3 mAb TS2/9) to TE cell surface LFA-3. Purified anti-LFA-3 mAb augmented IL-1 release in a concentration-dependent fashion. The anti-LFA-3-mediated augmentation of IL-1 release required both new protein and RNA synthesis as shown by the ability of cycloheximide and actinomycin-D to inhibit augmentation of IL-1 production by TE cells, and by direct quantitation of IL-1 alpha and IL-1 beta mRNA by Northern blot analysis. Both F(ab)'2 and Fab' fragments of anti-LFA-3 mAb augmented IL-1 alpha and IL-1 beta mRNA production, indicating that monovalent binding to cell surface LFA-3 was sufficient to provide the inducing signal. The identification of LFA-3, the cell surface ligand for thymocyte CD2 molecules, as a molecule via which TE cell-derived cytokine production may be regulated suggests a mechanism at the cell surface by which direct TE cell-thymocyte interaction might result in the triggering of local IL-1 release within the human thymic microenvironment.
我们已经证明，人胸腺上皮（TE）细胞可产生白细胞介素-1α（IL-1α）、白细胞介素-1β（IL-1β），并且TE细胞通过胸腺细胞上的CD2和淋巴细胞功能相关抗原-1（LFA-1）分子以及TE细胞上的淋巴细胞功能相关抗原-3（LFA-3）、细胞间黏附分子-1（ICAM-1）与胸腺细胞结合。我们研究了配体与人TE细胞上的LFA-3结合是否能调节TE细胞IL-1的产生。首先，我们研究了人胸腺细胞调节TE细胞释放IL-1的能力。自体和同种异源经依米丁处理的胸腺细胞与TE细胞共培养时，均可增强TE细胞IL-1的释放。IL-1释放的增强与细胞密度有关。由于胸腺细胞与TE细胞之间的相互作用部分是由胸腺细胞上的CD2分子和TE细胞上的LFA-3分子介导的，接下来我们确定配体（抗LFA-3单克隆抗体TS2/9）与TE细胞表面LFA-3结合对IL-1释放的影响。纯化的抗LFA-3单克隆抗体以浓度依赖的方式增强IL-1的释放。抗LFA-3介导的IL-1释放增强需要新的蛋白质和RNA合成，这可通过放线菌酮和放线菌素-D抑制TE细胞IL-1产生的增强能力以及通过Northern印迹分析直接定量IL-1α和IL-1β mRNA来证明。抗LFA-3单克隆抗体的F(ab)'2和Fab'片段均增强了IL-1α和IL-1β mRNA的产生，表明与细胞表面LFA-3的单价结合足以提供诱导信号。胸腺细胞CD2分子的细胞表面配体LFA-3被鉴定为一种可调节TE细胞衍生细胞因子产生的分子，这提示了一种细胞表面机制，通过该机制，TE细胞与胸腺细胞的直接相互作用可能导致人胸腺微环境中局部IL-1的释放触发。
