Kalies Kathrin, König Peter, Zhang Yong-Ming, Deierling Maria, Barthelmann Julia, Stamm Claudia, Westermann Jürgen
Centre for Structural and Cell Biology in Medicine, Institute of Anatomy, University of Luebeck, Luebeck, Germany.
J Immunol. 2008 Apr 15;180(8):5457-65. doi: 10.4049/jimmunol.180.8.5457.
The differentiation of CD4(+) T cells is regulated by cytokines locally within the compartments of secondary lymphoid organs during adaptive immune responses. Quantitative data about the expression of cytokine mRNAs within the T and B cell zones of lymphoid organs are lacking. In this study, we assessed the expression of multiple cytokine genes within the lymphoid compartments of the spleen of rats after two types of stimulation. First, the spleen was stimulated directly by a blood-derived Ag. Second, the spleen was stimulated indirectly by incoming lymphocytes that had been activated and released during a proceeding immune response at a distant tissue site. Using laser microdissection, we show that the expression of cytokine mRNAs was compartment specific, transient, and preceded cell proliferation after the direct antigenic stimulation. Surprisingly, the indirect stimulation by incoming activated lymphocytes induced similar cytokines in the T cell zone. However, the nonoverlapping expression was lost and IL10 appeared as the major cytokine in all compartments. Thus, tracking two types of immune activation without disturbing the integrity of structures reveals distinct and overlapping events in the compartments of the spleen. This information adds a new dimension to the understanding of immune responses in vivo.
在适应性免疫反应过程中，CD4(+) T细胞的分化由次级淋巴器官隔室内的细胞因子局部调节。目前缺乏关于淋巴器官T细胞和B细胞区内细胞因子mRNA表达的定量数据。在本研究中，我们评估了两种刺激后大鼠脾脏淋巴隔室内多种细胞因子基因的表达。首先，用血液来源的抗原直接刺激脾脏。其次，通过在远处组织部位先前的免疫反应中被激活并释放的传入淋巴细胞间接刺激脾脏。使用激光显微切割技术，我们发现细胞因子mRNA的表达具有隔室特异性、短暂性，并且在直接抗原刺激后先于细胞增殖出现。令人惊讶的是，传入的活化淋巴细胞的间接刺激在T细胞区诱导了类似的细胞因子。然而，非重叠表达消失，IL10在所有隔室中成为主要细胞因子。因此，在不干扰结构完整性的情况下追踪两种类型的免疫激活揭示了脾脏隔室内不同和重叠的事件。这些信息为理解体内免疫反应增添了新的维度。
