Suppression of the bacterial antigen-specific T cell response and the dendritic cell migration to the lymph nodes by osteopontin
Suppression of the bacterial antigen-specific T cell response and the dendritic cell migration to the lymph nodes by osteopontin
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DOI：
10.1111/j.1348-0421.2007.tb03884.x
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发表时间：
2007-01-01
影响因子：
2.6
通讯作者：
Matsuzaki, Goro
中科院分区：
文献类型：
--
作者：
Begum, Mst. Dilara;Umemura, Masayuki;Matsuzaki, Goro
骨桥蛋白（OPN）通过诱导白细胞介素（IL）-12和抑制IL-10来增强产生干扰素（IFN）-γ的Th 1型T细胞应答。因此，我们研究了OPN是否可以通过体内接种细菌抗原来增强Th 1诱导。出乎意料的是，OPN的共接种抑制了皮下热灭活单核细胞增生李斯特菌（HKLM）免疫后产生IFN-γ的CD 4（+）T细胞的诱导和T细胞增殖反应。这些结果表明，OPN下调T细胞引发。由于树突状细胞（DC）在T细胞引发中起关键作用，我们接下来分析了OPN对DC的作用。骨髓来源的未成熟DC或未成熟DC系JAWSII的培养物中加入OPN对HKLM刺激前后MHC II类、CD 80和CD 86分子的表达没有影响。结论OPN处理的DC对李斯特菌特异性Th 1型T细胞具有正常的抗原提呈功能。然而，当DC与HKLM和OPN一起转移到足垫时，与单独使用HKLM转移的DC相比，转移的DC向区域LN的迁移受到抑制。此外，OPN加入到DC系和HKLM的培养物中严重抑制了HKLM诱导的CCR 7趋化因子受体的表达，CCR 7趋化因子受体是DC迁移到LN中的重要因素。提示OPN通过调节DC迁移参与T细胞免疫应答的负反馈机制。
Osteopontin (OPN) has been reported to enhance the interferon (IFN)-gamma-producing Th1-type T cell response through the induction of interleukin (IL)-12 and the suppression of IL-10. We therefore investigated whether OPN could enhance Th1 induction by vaccination against bacterial antigen in vivo. Unexpectedly, the co-inoculation of OPN suppressed the induction of IFN-gamma-producing CD4(+) T cells and T cell proliferative response after the subcutaneous heat-killed Listeria monocytogenes (HKLM) immunization. These results suggest that OPN down-regulates T cell priming. Since dendritic cells (DC) play a pivotal role in T cell priming, we next analyzed the effects of OPN on DC. The addition of OPN into the culture of either bone marrow-derived immature DC or an immature DC line JAWSII showed no effects on the expression of MHC class II, CD80, and CD86 molecules before and after HKLM stimulation. Consistently, in vitro OPN-treated DC showed a normal antigen-presenting function to an established Listeria-specific Th1-type T cells. However, when the DC were transferred into the footpad with HKLM and OPN, the migration of the transferred DC into the regional LN was suppressed in comparison to the DC transferred with HKLM alone. Furthermore, the addition of OPN into the culture of the DC line and HKLM severely suppressed the HKLM-induced expression of CCR7 chemokine receptor which is an important factor in the migration of DC into LN. All the results suggest the existence of an OPN-mediated negative feedback mechanism in the T cell immune response through the regulation of DC migration.