Johansson Cecilia, Wick Mary Jo
Department of Cell and Molecular Biology, Section for Immunology, Lund University, Lund, Sweden.
J Immunol. 2004 Feb 15;172(4):2496-503. doi: 10.4049/jimmunol.172.4.2496.
The capacity of murine liver dendritic cells (DC) to present bacterial Ags and produce cytokines after encounter with Salmonella was studied. Freshly isolated, nonparenchymal liver CD11c(+) cells had heterogeneous expression of MHC class II and CD11b and a low level of CD40 and CD86 expression. Characterization of liver DC subsets revealed that CD8alpha(-)CD4(-) double negative cells constituted the majority of liver CD11c(+) ( approximately 85%) with few cells expressing CD8alpha or CD4. Flow cytometry analysis of freshly isolated CD11c(+) cells enriched from the liver and cocultured with Salmonella expressing green fluorescent protein (GFP) showed that CD11c(+) MHC class II(high) cells had a greater capacity to internalize Salmonella relative to CD11c(+) MHC class II(low) cells. Moreover, both CD8alpha(-) and CD8alpha(+) liver DC internalized bacteria with similar efficiency after both in vitro and in vivo infection. CD11c(+) cells enriched from the liver could also process Salmonella for peptide presentation on MHC class I and class II to primary, Ag-specific T cells after internalization requiring actin cytoskeletal rearrangements. Flow cytometry analysis of liver CD11c(+) cells infected with Salmonella expressing GFP showed that both CD8alpha(-) and CD8alpha(+) DC produced IL-12p40 and TNF-alpha. The majority of cytokine-positive cells did not contain bacteria (GFP(-)) whereas only a minor fraction of cytokine-positive cells were GFP(+). Furthermore, only approximately 30-50% of liver DC containing bacteria (GFP(+)) produced cytokines. Thus, liver DC can internalize and process Salmonella for peptide presentation to CD4(+) and CD8(+) T cells and elicit proinflammatory cytokine production upon Salmonella encounter, suggesting that DC in the liver may contribute to immunity against hepatotropic bacteria.
研究了小鼠肝脏树突状细胞（DC）在接触沙门氏菌后呈递细菌抗原和产生细胞因子的能力。新鲜分离的非实质肝脏CD11c(+)细胞具有MHC II类和CD11b的异质性表达以及低水平的CD40和CD86表达。肝脏DC亚群的特征表明，CD8α(-)CD4(-)双阴性细胞构成了肝脏CD11c(+)细胞的大部分（约85%），很少有细胞表达CD8α或CD4。对从肝脏富集并与表达绿色荧光蛋白（GFP）的沙门氏菌共培养的新鲜分离的CD11c(+)细胞进行流式细胞术分析表明，相对于CD11c(+) MHC II类（低）细胞，CD11c(+) MHC II类（高）细胞具有更强的内化沙门氏菌的能力。此外，在体外和体内感染后，CD8α(-)和CD8α(+)肝脏DC以相似的效率内化细菌。从肝脏富集的CD11c(+)细胞在需要肌动蛋白细胞骨架重排的内化后，也可以处理沙门氏菌，以便将肽呈递给MHC I类和II类上的初始抗原特异性T细胞。对感染表达GFP的沙门氏菌的肝脏CD11c(+)细胞进行流式细胞术分析表明，CD8α(-)和CD8α(+) DC均产生IL-12p40和TNF-α。大多数细胞因子阳性细胞不含细菌（GFP(-)），而只有一小部分细胞因子阳性细胞是GFP(+)。此外，只有约30-50%含有细菌（GFP(+)）的肝脏DC产生细胞因子。因此，肝脏DC可以内化和处理沙门氏菌，以便将肽呈递给CD4(+)和CD8(+) T细胞，并在遇到沙门氏菌时引发促炎细胞因子的产生，这表明肝脏中的DC可能有助于抵抗嗜肝细菌的免疫。
