The role of CD1d-restricted NK T lymphocytes in the immune response to oral infection with Salmonella typhimurium
The role of CD1d-restricted NK T lymphocytes in the immune response to oral infection with Salmonella typhimurium
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DOI：
10.1002/eji.200425846
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发表时间：
2005-07-01
影响因子：
5.4
通讯作者：
Cardell, SL
中科院分区：
文献类型：
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作者：
Berntman, E;Rolf, J;Cardell, SL
CD1d限制性自然杀伤T（NKT）细胞属于固有样淋巴细胞，能对压力和感染挑战迅速作出反应。我们研究了小鼠在口服感染致病性鼠伤寒沙门氏菌后的早期免疫应答中CD1d限制性NKT细胞的情况。在肝脏和脾脏中，感染后第5天中性粒细胞和巨噬细胞数量增加了几倍，而B淋巴细胞和T淋巴细胞的频率降低。这些细胞变化不依赖于CD1d限制性NKT细胞，而且CD1d限制性T细胞不影响细菌载量。然而，在CD1d（+）小鼠中，NK1.1（+）T细胞和恒定的CD1d限制性T细胞被感染激活，表现为细胞增大、CD69上调以及干扰素 -γ产生。在感染过程中，这些细胞上的NK1.1抗原下调，而T细胞受体水平不受影响。虽然树突状细胞（DC）在体外暴露于细菌24小时后CD1d水平上调，但在感染期间体内DC上CD1d表达增加并不明显。此外，对从感染小鼠中分离出的CD1d限制性T细胞进行体外再刺激，结果显示细胞因子谱发生显著偏移，白细胞介素 - 4受到抑制，干扰素 -γ产生增加。
CD1d-restricted natural killer T (NKT) cells belong to the innate-like lymphocytes which respond rapidly to stress and infectious challenge. We have studied murine CD1d-restricted NKT cells in the early immune response to virulent Salmonella enterica serovar Typhimurium after oral infection. In the liver and spleen, neutrophil and macrophage numbers had increased several-fold by day 5 post-infection, while the frequency of B and T lymphocytes decreased. These cellular changes occurred independently of CD1drestricted NKT cells, and further, CD1d-restricted T cells did not influence the bacterial load. However, in CD1d(+) mice NK1.1(+) T cells and invariant CD1d-restricted T cells were activated by the infection, as demonstrated by an increase in size, up-regulation of CD69 and production of IFN-gamma. The NK1.1 antigen was down-modulated on these cells during the course of infection, while TCR levels were unaffected. While dendritic cells (DC) upregulated CD1d-levels upon 24 h of in vitro exposure to the bacteria, increased CD1d expression was not evident on DC in vivo during infection. Furthermore, in vitro restimulation of CD1d-restricted T cells isolated from infected mice demonstrated a significant skewing of the cytokine profile, with suppressed IL-4 and increased IFN-gamma production.