Preexisting inflammation due to Mycobacterium bovis BCG infection differentially modulates T-cell priming against a replicating or nonreplicating immunogen
Preexisting inflammation due to Mycobacterium bovis BCG infection differentially modulates T-cell priming against a replicating or nonreplicating immunogen
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DOI：
10.1128/iai.70.4.1957-1964.2002
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发表时间：
2002-04-01
影响因子：
3.1
通讯作者：
Sad, S
中科院分区：
文献类型：
--
作者：
Dudani, R;Chapdelaine, Y;Sad, S
通过接种疫苗诱导T细胞记忆确保了对病原体的长期保护。我们确定了疫苗接种过程中持续的炎症反应是否影响T细胞的启动。将小鼠预先暴露在牛分枝杆菌卡介苗中，会削弱它们随后激发T细胞对抗单核细胞增多性李斯特菌的能力。这是以分泌单核细胞增多性乳杆菌特异性干扰素(干扰素-伽马)的CD4(+)和CD8(+)T细胞减少为特征的。T细胞对单核细胞增多性李斯特氏菌的刺激强度取决于单核细胞增多性李斯特氏菌的扩张程度，而卡介苗诱导的炎症引起的这种扩张的停止会导致T细胞的启动功能受损。用更高剂量的单核细胞增多性乳杆菌攻击牛分枝杆菌感染的小鼠，可增加单核细胞增多性乳杆菌的存活率，并恢复T细胞对单核细胞增多性乳杆菌的启动。单核细胞增多性李斯特氏菌诱导的炎症导致T细胞对单核细胞增多性李斯特氏菌免疫功能的破坏，导致小鼠在再次感染单核细胞增多性乳杆菌后的长期保护效果受损。预先存在的炎症选择性地损害了T细胞对复制免疫原的启动，因为CD8(+)T细胞对作为惰性抗原的卵清蛋白(卵清蛋白-考古体)的反应被BCG预免疫增强，而对作为活免疫原的卵清蛋白(单核细胞增生性卵白蛋白)的启动则受到损害。因此，根据免疫原的性质，先前炎症反应的存在可能会阻碍或增强疫苗的效力。
Induction of T-cell memory by vaccination ensures long-term protection against pathogens. We determined whether on-going inflammatory responses during vaccination influenced T-cell priming. A preexposure of mice to Mycobacterium bovis BCG impaired their subsequent ability to prime T cells against Listeria monocytogenes. This was characterized by a decrease in L. monocytogenes-specific gamma interferon (IFN-gamma)-secreting CD4(+) and CD8(+) T cells. The intensity of T-cell priming towards L. monocytogenes depended on the extent of L. monocytogenes expansion, and a cessation of this expansion caused by M. bovis BCG-induced inflammation resulted in impairment in T-cell priming. A challenge of M. bovis BCG-infected mice with a higher L. mono cytogenes dose increased L. monocytogenes survival and restored T-cell priming towards L. monocytogenes. Impairment in T-cell priming towards L. monocytogenes due to M. bovis BCG-induced inflammation resulted in a compromised protective efficacy in the long term after mice were rechallenged with L. monocytogenes. Preexisting inflammation selectively impaired T-cell priming for replicating immunogens as CD8(+) T-cell response to ovalbumin administered as an inert antigen (ovalbumin-archaeosomes) was enhanced by M. bovis BCG preimmunization, whereas priming towards ovalbumin administered as a live immunogen (L. monocytogenes-ovalbumin) was impaired. Thus, depending on the nature of the immunogen, the presence of prior inflammatory responses may either impede or boost vaccine efficacy.