Thomsen A R, Nansen A, Christensen J P, Andreasen S O, Marker O
Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark.
J Immunol. 1998 Nov 1;161(9):4583-90.
CD40 ligand (CD40L) is an important molecule that is known to be involved in T-B collaboration and certain aspects of cell-mediated immunity. However, its role in antiviral immunity has not been clearly defined as of yet. Therefore, mice with a targeted defect in the gene encoding this molecule were infected with one of two strains of lymphocytic choriomeningitis virus differing markedly in their capacity to spread in the host. Infection with lymphocytic choriomeningitis virus is initially controlled primarily by CD8+ effector cells, whereas long-term immune surveillance also depends upon CD4+ cells and B cells. Our results reveal that the primary activation, clonal expansion, and differentiation of CD8+ T cells does not require expression of CD40L. However, lack of expression results in rapid impairment of CTL responsiveness and failure to permanently control virus replication. This happens not only in mice infected with the rapidly spreading virus strain but also at a late stage in mice infected with the strain of more limited potential for spreading. In the latter mice, virus replication is initially controlled very efficiently, but high levels of virus can be detected in the blood and internal organs approximately 6 mo after virus inoculation. Since the impairment of immune function seems to be more pronounced in CD40L-deficient mice than in mice lacking either CD4+ cells or B cells, these results indicate that CD40L is pivotal to sustain efficient antiviral immune surveillance, including CD8+ T cells, and suggest that CD40L is critically involved in cellular interactions in addition to T-B cooperation.
CD40配体（CD40L）是一种重要分子，已知其参与T细胞与B细胞的协作以及细胞介导免疫的某些方面。然而，截至目前其在抗病毒免疫中的作用尚未明确界定。因此，将编码该分子的基因存在靶向缺陷的小鼠，用两种在宿主体内传播能力差异显著的淋巴细胞性脉络丛脑膜炎病毒株之一进行感染。淋巴细胞性脉络丛脑膜炎病毒感染最初主要由CD8 +效应细胞控制，而长期免疫监视也依赖于CD4 +细胞和B细胞。我们的结果显示，CD8 + T细胞的初始激活、克隆扩增和分化并不需要CD40L的表达。然而，缺乏表达会导致CTL反应性迅速受损，无法永久控制病毒复制。这不仅发生在感染快速传播病毒株的小鼠中，也发生在感染传播潜力较有限病毒株的小鼠的后期。在后者的小鼠中，病毒复制最初得到非常有效的控制，但在病毒接种后约6个月，可在血液和内脏器官中检测到高水平的病毒。由于免疫功能的损害在CD40L缺陷小鼠中似乎比在缺乏CD4 +细胞或B细胞的小鼠中更为明显，这些结果表明CD40L对于维持包括CD8 + T细胞在内的有效的抗病毒免疫监视至关重要，并表明CD40L除了参与T - B协作外，还在细胞相互作用中起关键作用。
