scholarly journals Response of the Splenic Dendritic Cell Population to Malaria Infection

2004 ◽  
Vol 72 (7) ◽  
pp. 4233-4239 ◽  
Author(s):  
Andrew L. Leisewitz ◽  
Kirk A. Rockett ◽  
Bonginkosi Gumede ◽  
Margaret Jones ◽  
Britta Urban ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cell Population ◽  
T Cell Activation ◽  
Malaria Infection ◽  
Cell Activation ◽  
Splenic Dendritic Cell ◽  
Dendritic Cell Population

ABSTRACT Dendritic cells, particularly those residing in the spleen, are thought to orchestrate acquired immunity to malaria, but it is not known how the splenic dendritic cell population responds to malaria infection and how this response compares with the responses of other antigen-presenting cells. We investigated this question for Plasmodium chabaudi AS infection in C57BL/6 mice. We found that dendritic cells, defined here by the CD11c marker, migrated from the marginal zone of the spleen into the CD4+ T-cell area within 5 days after parasites entered the bloodstream. This contrasted with the results observed for the macrophage and B-cell populations, which expanded greatly but did not show any comparable migration. Over the same time period dendritic cells showed upregulation of CD40, CD54, and CD86 costimulatory molecules that are required for successful T-cell activation. In dendritic cells, the peak intracellular gamma interferon expression (as shown by fluorescence-activated cell sorting) was on day 5, 2 days earlier than the peak expression in B-cells or macrophages. These findings show that splenic dendritic cells are actively engaged in the earliest phase of malarial infection in vivo and are likely to be critical in shaping the subsequent immune response.

scholarly journals DCision-making in tumors governs T cell anti-tumor immunity

Oncogene ◽  
2021 ◽  
Author(s):  
Francesca Alfei ◽  
Ping-Chih Ho ◽  
Wan-Lin Lo
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cancer Treatment ◽  
Tumor Immunity ◽  
T Cell Activation ◽  
Cell Activation ◽  
Genetic Alterations ◽  
Immune Checkpoint Blockade ◽  
Oncological Treatment

AbstractThe exploitation of T cell-based immunotherapies and immune checkpoint blockade for cancer treatment has dramatically shifted oncological treatment paradigms and broadened the horizons of cancer immunology. Dendritic cells have emerged as the critical tailors of T cell immune responses, which initiate and coordinate anti-tumor immunity. Importantly, genetic alterations in cancer cells, cytokines and chemokines produced by cancer and stromal cells, and the process of tumor microenvironmental regulation can compromise dendritic cell–T cell cross-talk, thereby disrupting anti-tumor T cell responses. This review summarizes how T cell activation is controlled by dendritic cells and how the tumor microenvironment alters dendritic cell properties in the context of the anti-tumor immune cycle. Furthermore, we will highlight therapeutic options for tailoring dendritic cell-mediated decision-making in T cells for cancer treatment.

TREM-1 modulates dendritic cell maturation and dendritic cell–mediated T cell activation induced by ox-LDL

2020 ◽  
Author(s):  
Yunkai Wang ◽  
Jie Wang ◽  
Lu Han ◽  
Yun Li Shen ◽  
Jie Yun You ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Human Peripheral Blood ◽  
Dendritic Cell Maturation ◽  
Cell Maturation ◽  
Blood Monocytes

Abstract Background: Triggering receptor expressed on myeloid cells (TREM)-1is identified as a major upstream proatherogenic receptor. However, the cellular processes modulated by TREM-1 in the development of atherosclerosis and plaque destabilization has not been fully elucidated. In this study, we investigated the effects of TREM-1 on dendritic cell maturation and dendritic cell–mediated T-cell activation induced by oxidized low-density lipoprotein (ox-LDL) in atherogenesis. Methods: Human peripheral blood monocytes were differentiated to dendritic cells and stimulated by ox-LDL. Naive autologous T cells were co-cultured with pretreated dendritic cells.The expressionof TREM-1 and the production of inflammatory cytokines were assessed by real-time PCR, western blot and ELISA.The expression of immune factors was determined with FACS to evaluate dendritic cell maturation and T-cell activation. Results: Stimulation with ox-LDL promoted dendritic cell maturation, TREM-1 expression and T-cell activation, and exposure of T cells to ox-LDL-treated dendritic cells induced production of interferon-γ and IL-17. Blocking TREM-1 suppressed dendritic cell maturation with low expression of CD1a, CD40, CD86 and HLA-DR, decreased production of TNF-α, IL-1β, IL-6 and MCP-1, and increased secretion of TGF-β and IL-10. In addition, stimulation of ox-LDL induced miR-155, miR-27, Let-7c and miR-185 expression, whereas inhibition of TREM-1 repressed miRNA-155. Silencing TREM-1 or miRNA-155 increased SOCS1 expression induced by ox-LDL. T cells derived from carotid atherosclerotic plaques or healthy individuals showed similar result patterns. Conclusion: These data suggest that TREM-1 modulates maturation of dendritic cells and activation of plaque T cells induced by ox-LDL, a pivotal player in atherogenesis.

scholarly journals Acidosis-Induced TGF-β2 Production Promotes Lipid Droplet Formation in Dendritic Cells and Alters Their Potential to Support Anti-Mesothelioma T Cell Response

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1284
Author(s):  
Natalia Trempolec ◽  
Charline Degavre ◽  
Bastien Doix ◽  
Davide Brusa ◽  
Cyril Corbet ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Lipid Droplet ◽  
T Cell Activation ◽  
Cell Response ◽  
Cell Activation ◽  
Transforming Growth Factor ◽  
T Cell Response ◽  
Mesenchymal Transition

For poorly immunogenic tumors such as mesothelioma there is an imperious need to understand why antigen-presenting cells such as dendritic cells (DCs) are not prone to supporting the anticancer T cell response. The tumor microenvironment (TME) is thought to be a major contributor to this DC dysfunction. We have reported that the acidic TME component promotes lipid droplet (LD) formation together with epithelial-to-mesenchymal transition in cancer cells through autocrine transforming growth factor-β2 (TGF-β2) signaling. Since TGF-β is also a master regulator of immune tolerance, we have here examined whether acidosis can impede immunostimulatory DC activity. We have found that exposure of mesothelioma cells to acidosis promotes TGF-β2 secretion, which in turn leads to LD accumulation and profound metabolic rewiring in DCs. We have further documented how DCs exposed to the mesothelioma acidic milieu make the anticancer vaccine less efficient in vivo, with a reduced extent of both DC migratory potential and T cell activation. Interestingly, inhibition of TGF-β2 signaling and diacylglycerol O-acyltransferase (DGAT), the last enzyme involved in triglyceride synthesis, led to a significant restoration of DC activity and anticancer immune response. In conclusion, our study has identified that acidic mesothelioma milieu drives DC dysfunction and altered T cell response through pharmacologically reversible TGF-β2-dependent mechanisms.

scholarly journals Distinct Roles of Dendritic Cells and B Cells in Va14Ja18 Natural T Cell Activation In Vivo

2005 ◽  
Vol 174 (8) ◽  
pp. 4696-4705 ◽  
Author(s):  
Jelena S. Bezbradica ◽  
Aleksandar K. Stanic ◽  
Naoto Matsuki ◽  
Helene Bour-Jordan ◽  
Jeffrey A. Bluestone ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
T Cell Activation ◽  
Cell Activation

DOCK8-Deficient Mice Reveal a Crucial Role for Dendritic Cell Activity in the Initiation of the Allogeneic Response to Transfused Red Blood Cells

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 658-658
Author(s):  
Stephanie C. Eisenbarth ◽  
Jeanne E. Hendrickson ◽  
Samuele Calabro ◽  
Antonia Gallman
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Innate Immune ◽  
Allogeneic Response ◽  
Deficient Mice

Abstract The generation of antibodies against transfused red blood cells (RBCs) can pose a serious health risk, especially in chronically transfused patients requiring life-long transfusion support; yet our understanding of what immune signals or cells dictate when someone will become alloimmunized is lacking. The relative role of dendritic cells, B cells and macrophages in the induction of RBC alloimmunization remain unclear. Given the now well established role of innate immune signals in regulating adaptive immunity, understanding if and how innate immunity is triggered during transfusion may allow development of therapies to prevent alloimmunization in chronically transfused subjects such as those with myelodysplasia or hemoglobinopathies. We have established a murine model system in which we can evaluate both the role of particular innate immune stimuli as well as particular cells of the immune system in regulating the allogeneic response to transfused RBCs. A particularly useful transgenic "HOD mouse" has been engineered, which encodes a triple fusion protein and provides a unique tool to directly assess both RBC-specific T and B cell responses. This RBC-specific antigen contains the model protein antigen hen egg lysozyme (HEL) fused to chicken ovalbumin (OVA) fused to the human Duffyb blood group antigen (HEL-OVA-Duffy) as an integral membrane protein under control of the beta globin promoter. Transfusion of genetically targeted mice lacking various innate immune cells or receptors allows us to screen for important immune pathways regulating the response to allogeneic RBCs. Using these models, we recently discovered that mice lacking the GEF (guanine nucleotide exchange factor) DOCK8 fail to develop alloimmunity to transfused RBCs. Dendritic cells in these knockout mice fail to migrate to T cells due to lack of coordinated actin rearrangement governed by this GEF. Both B cell and T cell activation in the spleen to the transgenic transfused RBCs is abrogated. Inclusion of OVA in the alloantigen of the HOD mice allows us to readily study naïve CD4+ T cell activation following transfusion by using the OTII T cell receptor (TCR) transgenic mice in which essentially all T cells express one antigen receptor specific for a peptide of OVA. By tracking rounds of cell division we found that adoptively transferred OTII undergo more than 5-8 rounds of division in the spleen three days following transfusion of HOD RBCs in WT recipients. In contrast, no OTII proliferation was observed in DOCK8-deficient mice following OTII adoptive transfer and HOD RBC transfusion, suggesting that T cells are failing to receive activation signals by splenic antigen presenting cells. Our preliminary data now suggest that DOCK8-deficient dendritic cells are able to process and present RBC-derived antigens, but do not migrate to T cell zones in the spleen to prime naïve RBC-specific T cells. The need for dendritic cell migration within the spleen in the induction of alloimmunity to transfused RBCs has not been addressed; these mice allow us for the first time to answer these fundamental immunologic questions during transfusion. Future work will aim to determine how dendritic cell movement within the spleen is regulated during transfusion and the specific role of splenic dendritic cell subsets in CD4+ T cell priming to allogeneic RBCs. Disclosures No relevant conflicts of interest to declare.

Modeling HIV transfer between dendritic cells and T cells: importance of HIV phenotype, dendritic cell– T cell contact and T-cell activation

AIDS ◽  
2000 ◽  
Vol 14 (15) ◽  
pp. 2299-2311 ◽  
Author(s):  
Guido Vanham ◽  
Lieve Penne ◽  
Heidi Allemeersch ◽  
Luc Kestens ◽  
Betty Willems ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Contact

scholarly journals Plasmacytoid Dendritic Cells Take Up Opsonized Antigen Leading to CD4+and CD8+T Cell Activation In Vivo

2008 ◽  
Vol 181 (6) ◽  
pp. 3811-3817 ◽  
Author(s):  
Pia Björck ◽  
Andreas Beilhack ◽  
Edward I. Herman ◽  
Robert S. Negrin ◽  
Edgar G. Engleman
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Plasmacytoid Dendritic Cells

Differentiation of myeloid dendritic cells into CD8α-positive dendritic cells in vivo

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1865-1872 ◽  
Author(s):  
Miriam Merad ◽  
Lawrence Fong ◽  
Jakob Bogenberger ◽  
Edgar G. Engleman
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Wild Type Mouse ◽  
Interleukin 12 ◽  
Myeloid Dendritic Cells ◽  
Myeloid Antigens

Bone marrow-derived dendritic cells (DC) represent a family of antigen-presenting cells (APC) with varying phenotypes. For example, in mice, CD8α+ and CD8α− DC are thought to represent cells of lymphoid and myeloid origin, respectively. Langerhans cells (LC) of the epidermis are typical myeloid DC; they do not express CD8α, but they do express high levels of myeloid antigens such as CD11b and FcγR. By contrast, thymic DC, which derive from a lymphoid-related progenitor, express CD8α but only low levels of myeloid antigens. CD8α+ DC are also found in the spleen and lymph nodes (LN), but the origin of these cells has not been determined. By activating and labeling CD8α− epidermal LC in vivo, it was found that these cells expressed CD8α on migration to the draining LN. Similarly, CD8α− LC generated in vitro from a CD8 wild-type mouse and injected into the skin of a CD8αKO mouse expressed CD8α when they reached the draining LN. The results also show that CD8α+ LC are potent APC. After migration from skin, they localized in the T-cell areas of LN, secreted high levels of interleukin-12, interferon-γ, and chemokine-attracting T cells, and they induced antigen-specific T-cell activation. These results demonstrate that myeloid DC in the periphery can express CD8α when they migrate to the draining LN. CD8α expression on these DC appears to reflect a state of activation, mobilization, or both, rather than lineage.

Sign in / Sign up

Export Citation Format

Share Document