Kronin V, Fitzmaurice C J, Caminschi I, Shortman K, Jackson D C, Brown L E
Cooperative Research Center for Vaccine Technology, Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3052, Australia.
Int Immunol. 2001 Apr;13(4):465-73. doi: 10.1093/intimm/13.4.465.
Dendritic cells (DC), in their role in initiation of the adaptive immune response, have been extensively studied for their capacity to interact and stimulate naive T cells. Subsets of mature murine DC isolated directly from the spleen have been shown to differ in their ability to induce proliferative responses in both primary CD4(+) and primary CD8(+) T cells; the myeloid-related CD8alpha(-) DC induce a more intense or prolonged proliferation of naive T cells than do the lymphoid-related DC bearing CD8alpha despite similar expression of MHC and co-stimulatory molecules. Here we examine the interaction of these DC subpopulations with T cells already in the activated or memory state which are known to have greater sensitivity to antigen stimulation and bear receptors with increased capacity for signal transduction. We show that influenza virus-specific CD4(+) T cell clones and splenic T cells from peptide-primed animals proliferated in response to antigen presented by separated splenic CD8(-) DC. In contrast, these T cells showed only weak, if any, proliferation in response to CD8(+) DC despite observable cluster formation in the cultures. The differential between the two DC types in inducing proliferation was even more pronounced than previously seen with primary T cells and did not reflect differential longevity of the DC in culture, altered response kinetics or deviation from IL-2 to IL-4 induction with CD8(+) DC, but was related to the levels of IL-2 induced. The deficiency in the CD8(+) DC was not overcome by using infectious virus rather than synthetic peptide as the antigen source. These results show that lymphoid-related CD8(+) splenic DC, despite their mature phenotype, fail to provide appropriate signals to secondary CD4(+) T cells to sustain their proliferation.
树突状细胞（DC）在启动适应性免疫反应中发挥作用，因其与幼稚T细胞相互作用并刺激其增殖的能力而受到广泛研究。直接从脾脏分离的成熟小鼠DC亚群在诱导原代CD4(+)和原代CD8(+) T细胞增殖反应的能力上存在差异；与髓样相关的CD8α(-) DC比带有CD8α的淋巴样相关DC能诱导幼稚T细胞更强烈或更持久的增殖，尽管它们的主要组织相容性复合体（MHC）和共刺激分子表达相似。在此，我们研究了这些DC亚群与已处于活化或记忆状态的T细胞之间的相互作用，已知这些T细胞对抗原刺激更敏感，且其受体的信号转导能力增强。我们发现，来自肽致敏动物的流感病毒特异性CD4(+) T细胞克隆和脾T细胞，对分离的脾CD8(-) DC呈递的抗原产生增殖反应。相比之下，尽管在培养物中可观察到细胞簇形成，但这些T细胞对CD8(+) DC的反应即使有也很微弱。两种DC类型在诱导增殖方面的差异比之前在原代T细胞中观察到的更为明显，且这并非反映DC在培养中的寿命差异、反应动力学改变或从白细胞介素-2（IL-2）诱导转向IL-4诱导，而是与诱导产生的IL-2水平有关。使用感染性病毒而非合成肽作为抗原来源并不能克服CD8(+) DC的缺陷。这些结果表明，淋巴样相关的脾CD8(+) DC尽管具有成熟的表型，但无法为继发性CD4(+) T细胞提供适当的信号以维持其增殖。
