While in vitro observations suggest that cross-presentation of antigens is mediated primarily by CD8α + dendritic cells, in vivo analysis has been hampered by the lack of systems that selectively eliminate this cell lineage. Here we show that deletion of the transcription factor Batf3 ablated development of CD8α + dendritic cells, allowing us to examine their role in immunity in vivo. Dendritic cells from Batf3 -/-mice were defective in cross-presentation and Batf3 -/-mice lacked virusspecific CD8 + T cell responses to West Nile virus. Importantly, rejection of highly immunogenic syngeneic tumors was impaired in Batf3 -/-mice. These results suggest an important role for CD8α + dendritic cells and cross-presentation in responses to viruses and in tumor rejection.During antigen 'cross-presentation' (1), antigens generated in one cell are presented by MHC class I molecules of a second cell. It remains unclear whether all antigen presenting cells (APCs) use cross-presentation and whether this pathway plays a role in immune responses in vivo (2). Dendritic cells (DCs) are a heterogeneous group of APCs with two major subsets, plasmacytoid dendritic cells (pDCs) and conventional CD11c + dendritic cells (cDCs) (3). Subsets of cDCs include CD8α + , CD4 + , and CD8α -CD4 -populations that may exert distinct functions in immune responses. Evidence has suggested that CD8α + cDCs are important for cross-presentation during infections, but is based on ex vivo analysis (4-6) or in vitro antigen loading (7). Evidence both for and against a role for cross-presentation in responses against tumors has been reported (8-10).Attempts have been made to study the in vivo role of dendritic cells by selective depletion. Diphtheria toxin treatment can deplete all CD11c hi cells in one transgenic mouse model (11), but affects splenic macrophages and activated CD8 + T cells (12). Gene targeting of transcription factors (e.g., Irf2, Irf4, Irf8, Stat3 and Id2) has caused broad defects in several DC subsets, T cells and macrophages (13). To identify genes regulating DC development, we performed global gene expression analysis across many tissues and immune cells ( fig S1A). Batf3 (p21SNFT) (14) was highly expressed in cDCs, with low to absent expression in other *To whom correspondence should be addressed. E-mail murphy@pathology.wustl.edu. fig. S1B-D).In spleens of Batf3 -/-mice we found a selective loss of CD8α + cDCs, without abnormalities in other hematopoietic cell types or architecture (Fig. 1, fig. S2-S11). CD8α + cDC coexpress DEC205, CD24, and low levels of CD11b (3,15). Batf3 -/-mice lacked splenic CD11c hi CD8α + DEC205 + cells (Fig. 1A), showed a loss of CD11c hi CD11b dull cells and CD11c hi CD8α + CD24 + cells (Fig. 1B), but had normal populations of CD4 + and CD8α -CD4 -cDC subsets (Fig. 1B). Lymph nodes and thymi of Batf3 -/-mice lacked CD8α + DCs but had normal distributions of CD8α -CD11c + cells (Fig. 1C). DEC205 int and DEC205 hi DCs were present in lymph nodes draining the skin of Batf3 -/-mice (Fig. 1C), and show...
Although CD103-expressing dendritic cells (DCs) are widely present in nonlymphoid tissues, the transcription factors controlling their development and their relationship to other DC subsets remain unclear. Mice lacking the transcription factor Batf3 have a defect in the development of CD8α+ conventional DCs (cDCs) within lymphoid tissues. We demonstrate that Batf3−/− mice also lack CD103+CD11b− DCs in the lung, intestine, mesenteric lymph nodes (MLNs), dermis, and skin-draining lymph nodes. Notably, Batf3−/− mice displayed reduced priming of CD8 T cells after pulmonary Sendai virus infection, with increased pulmonary inflammation. In the MLNs and intestine, Batf3 deficiency resulted in the specific lack of CD103+CD11b− DCs, with the population of CD103+CD11b+ DCs remaining intact. Batf3−/− mice showed no evidence of spontaneous gastrointestinal inflammation and had a normal contact hypersensitivity (CHS) response, despite previous suggestions that CD103+ DCs were required for immune homeostasis in the gut and CHS. The relationship between CD8α+ cDCs and nonlymphoid CD103+ DCs implied by their shared dependence on Batf3 was further supported by similar patterns of gene expression and their shared developmental dependence on the transcription factor Irf8. These data provide evidence for a developmental relationship between lymphoid organ–resident CD8α+ cDCs and nonlymphoid CD103+ DCs.
Graphene nanosheet (GNS) gives rise to an extraordinary modification to the properties of Pt cluster electrocatalysts supported on it. The Pt/GNS electrocatalyst revealed an unusually high activity for methanol oxidation reaction compared to Pt/carbon black catalyst. The Pt/GNS electrocatalyst also revealed quite a different characteristic for CO oxidation among the measured catalyst samples. It is found that Pt particles below 0.5 nm in size are formed on GNS, which would acquire the specific electronic structures of Pt, modifying its catalytic activities.
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