Characterization of the systemic loss of dendritic cells in murine lymph nodes during polymicrobial sepsis

Characterization of the systemic loss of dendritic cells in murine lymph nodes during polymicrobial sepsis
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DOI:
10.4049/jimmunol.173.5.3035
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发表时间:
2004-09-01
影响因子:
4.4
通讯作者:
Moldawer, LL
Moldawer, LL
中科院分区:
医学2区
文献类型:
--
作者:
Efron, PA;Martins, A;Moldawer, LL

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树突状细胞(DC)在危重病中起关键作用,并且在脓毒症患者和小鼠的脾脏中耗尽。迄今为止,很少有研究表征了脓毒症对淋巴组织中DC群体的全身效应。我们分析了诱导多微生物败血症(盲肠结扎和穿刺)小鼠的局部(肠系膜)和远端(腹股沟和腘)淋巴结中存在的DO和Th细胞的表型。流式细胞术和免疫组织化学染色表明,有一个显着的局部(肠系膜淋巴结)和部分系统(腹股沟,但不是腘淋巴结)的DC从脓毒症小鼠淋巴结的损失,这一过程与细胞凋亡增加。这种脓毒症诱导的DO丧失发生在淋巴结中的CD 3(+)CD 4(+)T细胞活化和丧失之后,并且DO丧失之前没有其成熟状态的任何持续增加。此外,在脓毒症期间,成熟/活化(MHCI高/CD 86(高))或未成熟(MHCI低/CD 86(低))DO没有优先损失。然而,局部和远处淋巴结中CD 8(+)DC优先丢失。淋巴组织,特别是CD 8(+)淋巴细胞来源的DC中DO的缺失可能导致获得性免疫状态的改变,这种改变经常伴随脓毒症。
Dendritic cells (DCs) play a key role in critical illness and are depleted in spleens from septic patients and mice. To date, few studies have characterized the systemic effect of sepsis on DC populations in lymphoid tissues. We analyzed the phenotype of DO and Th cells present in the local (mesenteric) and distant (inguinal and popliteal) lymph nodes of mice with induced polymicrobial sepsis (cecal ligation and puncture). Flow cytometry and immunobistochemical staining demonstrated that there was a significant local (mesenteric nodes) and partial systemic (inguinal, but not popliteal nodes) loss of DCs from lymph nodes in septic mice, and that this process was associated with increased apoptosis. This sepsis-induced loss of DO occurred after CD3(+)CD4(+) T cell activation and loss in the lymph nodes, and the loss of DO was not preceded by any sustained increase in their maturation status. In addition, there was no preferential loss of either mature/activated (MHCIIhigh/CD86(high)) or immature (MHCIIlow/CD86(low)) DO during sepsis. However, there was a preferential loss of CD8(+) DCs in the local and distant lymph nodes. The loss of DO in lymphoid tissue, particularly CD8(+) lymphoid-derived DCs, may contribute to the alterations in acquired immune status that frequently accompany sepsis.