Project description:Transcriptional profiles of four different myeloid antigen presenting cell (APC) subsets (BDCA-1+ circulating myeloid dendritic cells, CD14+ monocytes, and in vitro generated immature and mature monocyte-derived dendritic cells) were used for comprehensive transcriptome analysis. Based on the gene expression profiling data, a quantitative relationship between myeloid APC in functionally related gene spaces was established. Keywords = myeloid antigen presenting cells Keywords = dendritic cell subsets Keywords: repeat sample
Project description:Dr. van Kooyk's laboratory is exploring the function of antigen presenting cells, such as dendritic cells (DC), that regulate viral-antigen recognition, DC trafficking and T cell binding--all processes that initiate immunity or tolerance. Essential in this is the recognition of ligands by C-type lectins and the functional consequences of differential terminal glycosylation that may regulate DC function. In this study, the gene expression profile of glycosylation-related genes is examined in relation to the maturation of human antigen-presenting cells. Two pooled RNA samples, one each from immature and mature human monocyte-derived dendritic cells, were prepared and sent to Microarray Core (E). The RNA was amplified, labeled, and hybridized to the GLYCOv3 microarrays.
Project description:Dr. van Kooyk's laboratory is exploring the function of antigen presenting cells, such as dendritic cells (DC), that regulate viral-antigen recognition, DC trafficking and T cell binding--all processes that initiate immunity or tolerance. Essential in this is the recognition of ligands by C-type lectins and the functional consequences of differential terminal glycosylation that may regulate DC function.
Project description:This trial is to compare the efficacy and safety of modified FOLFOX6 [mFOLFOX6, a specific chemotherapy regimen of Oxaliplatin ,5-Fluorouracil and Leucovorin] chemotherapy plus Antigen Pulsed Dendritic Cells (APDC,a kind of autologous tumor lysates pulsed human dendritic cells vaccine) with modified chemotherapy alone in patients with metastatic colorectal cancer.
Project description:Antigen presenting dendritic cells (DCs) and monocytes capture and transport antigens from barrier tissues for presentation to antigen-specific T cells in the draining-lymph nodes (LNs). While DCs enter LNs through afferent lymphatics in a CCR7-dependent manner, how exactly antigen-carrying monocytes reach LNs is less clear since monocytes do not express CCR7 and can also enter LNs via the bloodstream. In steady state, and following injection of several PAMPs, scRNA-seq data on LN mononuclear phagocytes identified LN resident versus migratory type 1 and type 2 conventional (c)DCs despite downregulation of DC subset-defining transcripts, such as Xcr1, Clec9a, H2-Ab1, Sirpa, and Clec10a on migratory cDCs. Migratory cDCs gained expression of transcripts controlling cellular migration such as Ccr7, Ccl17, Ccl22, and Ccl5, while migratory monocytes expressed Ccr5 without Ccr7. Using two tracking methods and a gating strategy that clearly distinguishes migratory CD88hiCD26lo monocytes from CD88-CD26hi cDCs, we found that both captured antigens in the lung and migrated to lung-draining LNs. Using global and mixed-chimeric Ccl5-, Ccr2-, Ccr5-, Ccr7-, and Batf3-deficient mice, we found that CCR5+ monocytes follow CCL5-secreting migratory cDCs to reach the draining LN via lymphatic vessels. In a model of asthma, such recruited monocytes regulated the induction of type 2 immunity. Overall, our data suggest that CCL5-secreting migratory cDCs lay down the chemokine trail for CCR5+ antigen-presenting monocytes to reach draining lymph nodes and regulate adaptive immunity.
Project description:Plasmacytoid dendritic cells (pDCs) play a crucial role in orchestrating immune responses, especially against viral infections, and have traditionally been well recognized for their ability to produce type I and type III interferons. However, recent discoveries reveal pDCs to be heterogeneous with more complex functions that include antigen uptake, processing, and presentation. We investigated the antigen cross-presentation ability of pDCs and their role in CD8+ T cell priming, a subject of ongoing debate. Utilizing a novel culturing system of CD8+ T cells and autologous pDCs derived from human blood circulating CD34+ hematopoietic stem and progenitor cells (cHSPCs), we demonstrate that pDCs can efficiently prime CD8+ T cells through cross-presentation, thereby contributing to their expansion and cytotoxic activity. The pDCs’ antigen presentation ability is comparable to that of monocyte-derived dendritic cells (moDCs), which are traditionally known for their efficient antigen presentation capacity. Bioinformatic analysis of the primed CD8+ T cells to uncover their transcriptomic profile following priming by pDCs versus moDCs, revealed distinct genetic signatures, indicating that pDCs prime CD8+ T cells differently than cDCs. These findings challenge the traditional view of pDCs as mere IFN-producing cells, highlighting their significant role in antigen presentation and T cell activation.
Project description:Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. As such they are currently used in clinical vaccination protocols in cancer patients. We evaluate the ability of mature DCs pulsed with carcinoembryonic antigen (CEA)-peptide (arm A) or electroporated with CEA-mRNA (arm B) to induce CEA-specific T cell responses in patients with resectable liver metastases from colorectal cancer. To evaluate immune responses, CEA-specific T cell reactivity is monitored in peripheral blood, resected abdominal lymph nodes, tumor tissue and biopsies of vaccination sites and post-treatment DTH skin tests. Patients are vaccinated intradermally and intravenously with CEA-peptide pulsed mature DCs three times prior to resection of liver metastases. In 2007 a side-study has been added (arm C), in which patients with stage III or high-risk stage II colorectal cancer that are amenable for standard adjuvant oxaliplatin/capecitabine therapy are vaccinated with CEApeptide-pulsed DCs. Also in this group, safety and immune responses in peripheral blood and the DTH-skin test are the primary endpoints. Results are compared with the results obtained in arm A.