Dramatic increase in lymph node dendritic cell number during infection by the mouse mammary tumor virus occurs by a CD62L-dependent blood-borne DC recruitment

Abstract

IntroductionDendritic cells (DCs) play a central role in the immune system due to their main function as initiators and regulators of antigenspecific antiviral T-cell responses and in the pathogenesis of a variety of viruses, such as human immunodeficiency virus (HIV), cytomegalovirus, measles virus, herpes virus, influenza virus, and respiratory syncytial virus. 1 However, little is known about the subpopulations of DCs involved in antiviral responses, the kinetics of the variations of DC subpopulations, and, importantly, the mechanisms of recruitment of DCs to the lymph nodes (LNs) during inflammatory responses driven by viral infections. On the other hand, despite the available information dealing with the phenotype and function of the 2 main mouse DC subsets, namely, CD8 Ϫ and CD8 ϩ DCs, their involvement in antiviral immune responses in vivo as well as their functional relationships and origin remain largely unknown.Over the last years CD8 Ϫ and CD8 ϩ DCs have been ascribed to the myeloid and lymphoid lineages, respectively, and consequently considered as independent DC categories. 1 However, more recently 2 reports from our group and Dr Weissman's laboratory (Stanford University) have described the generation of both CD8 Ϫ and CD8 ϩ DCs from a common lymphoid precursor 2 or from either myeloidor lymphoid-committed precursors. 3 These results suggest that in fact CD8 Ϫ and CD8 ϩ DCs might not represent independent cell types, and in this sense we have previously reported that migrationor CD40L ligation-induced Langerhans cell (LC) maturation involved CD8 up-regulation. 4,5 In these reports, which have been confirmed by a recent article by Merad et al, 6 we showed that the LN-restricted CD8 int DC population derived from LCs. 4,5 On the basis of these previous data on LN DCs and using the dramatic changes occurring in the draining popliteal LNs (PO-LNs) after infection by the Swiss (SW) strain of the mouse mammary tumor virus (MMTV), 7 we have extensively analyzed the mechanisms of DC recruitment during the inflammatory responses induced by a viral infection as well as the relationships between the different DC subsets involved. The results presented here indicate that MMTV(SW) induces a strong migration of blood-borne CD8 Ϫ DCs to the PO-LNs via high endothelial venules (HEVs), providing direct evidence of DC recruitment to the LNs during an in vivo viral infection-driven inflammatory process. Moreover, our data strongly suggest that LN CD8 ϩ DCs originate as the result of CD8 up-regulation by LN CD8 Ϫ DCs, supporting the view that these subsets represent different physiologic states of the same DC population. Finally, the fact that DCs become infected by MMTV(SW) suggest their participation in the immune response against this virus. Materials and methods Experimental infection with MMTV(SW)The MMTV(SW) was purified from milk and titered as described previously. 8 Eight-to 10-week-old BALB/c mice were given a 10-L injection Supported by the European Commission (grant no. QLRT-1999-00276) For personal use on...

The Duration of Signaling through CD40 Directs Biological Ability of Dendritic Cells to Induce Antitumor Immunity

“…Thus, it is likely that the expression of CCR7 accounts for the augmented migration of 3h-DCs and reduced migration of 24h-DCs. Although it was reported that CD62L, which recognizes high endothelial venules, plays an important role in the migration of DCs to secondary lymphoid organs (46), no expression of CD62L was detected on DCs stimulated for 0, 3, or 24 h with immobilized anti-CD40 Ab (data not shown). Subcutaneous inoculation of 3h-DCs induced a marked increase in the total number of cells and the percentage of Ag-primed T cells, which were depicted as T cells with down-regulated CD62L expression, in the draining LNs (Figs.…”

Critical Role of Dendritic Cells in Mouse Mammary Tumor Virus In Vivo Infection

“…Indeed, MMTV has been shown to interact with DCs. Both experimental subcutaneous inoculation with MMTV and milk-borne infection produce dramatic increases in the numbers of DCs in the draining lymph nodes and Peyer's patches, respectively (8,24). In addition, DCs can be infected by MMTV and can present Sag to T cells, suggesting their involvement in the early phase of infection (5,24,38).…”

“…Both experimental subcutaneous inoculation with MMTV and milk-borne infection produce dramatic increases in the numbers of DCs in the draining lymph nodes and Peyer's patches, respectively (8,24). In addition, DCs can be infected by MMTV and can present Sag to T cells, suggesting their involvement in the early phase of infection (5,24,38). Finally, it has been demonstrated that MMTV can induce DC maturation and up-regulation of surface expression of the virus entry receptor transferrin receptor 1 (TfR1) via interaction with Toll-like receptor 4 (TLR4) (8).…”

Mast Cells, Histamine, and IL-6 Regulate the Selective Influx of Dendritic Cell Subsets into an Inflamed Lymph Node

“…Infection leads to the recruitment of pDCs and CD8 + DCs into the draining lymph node from the blood (32)(33)(34)43). The influx of pDC is dependent on b 1 -and b 2 -integrins, CXCL9 and E-selectin Data are mean number of cells per lymph node 6 SE based on 10-15 mice/group from two to three independent experiments.…”