In this study, we generated a chimeric situation by injection of different gene-modified BM-DCs into different strains of gene-modified recipient mice. This allowed us to identify the separate functional contributions of injected versus endogenous DCs for Th1 polarization. We identified the cellular source of IL-12p70 production after subcutaneous BM-DC vaccination as endogenous migratory XCR1+ bystander DCs in the skin draining lymph nodes. DC-DC and DCT cell interaction studies revealed a time course of Th0 priming by injected BM-DCs, followed by interactions of BM-DC with the IL-12+ XCR1+ bystander DCs, and finally IL-12+ XCR1+ bystander DC interactions for Th1 induction. Transcriptional profiling of the bystander DCs underscores their Th1 polarization potential. Together, this study shows that DC-vaccination requires the bystander activation of endogenous DCs for Th1 priming. Our data also challenge the general concept of Th1 priming by a single DC providing all signals 1, 2 and 3 to T cells for Th1 polarization. SOURCE: Tobias Heckel (ht-seq.sysmed@uni-wuerzburg.de) - Raum D15.02.045 University of Wuerzburg

Pluto Bioinformatics

GSE124677: IL-12 From Endogenous cDC1, and Not Vaccine DC, Is Required for Th1 Induction