Antigen-presenting Cell Subtypes Research Articles

Lung CD103+ Dendritic cells of mice infected with Paracoccidioides brasiliensis contribute to Treg differentiation

The DC subsets that express αE integrin (CD103) have been described to exert antagonistic functions, driving T cells towards either an inflammatory (Th1/Th17) or immunosuppressive phenotype (regulatory T cells - Treg). These functions depend on the tissue they reside and microenvironment factors or stimuli that this Antigen-presenting cell (APC) subpopulation receive. In this regard, immunoregulatory phenotype has been described in small subsets of CD103+ DCs from lung and intestinal mucosa. The function of this APC subpopulation in pulmonary Paracoccidioides brasiliensis infection is poorly described. Here, we showed that lung CD103+ DCs contribute to Treg differentiation in a pulmonary P. brasiliensis infection model, which was attributed to downregulation of costimulatory molecules analyzed in these APC subtypes 21 days post-infection. Overall, this data suggests that P. brasiliensis infection caused an immunosuppression that has also been observed in patients with the most severe form of Paracoccidioidomycosis (PCM) – a sickness caused by this fungus genus. Furthermore, these results open new perspectives for knowledge of the mechanisms that underlie the higher percentage of Treg cells found in peripheral blood of PCM patients.

Dichotomous Expression of TNF Superfamily Ligands on Antigen-Presenting Cells Controls Post-priming Anti-viral CD4+ T Cell Immunity

T cell antigen-presenting cell (APC) interactions earlyduring chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITRis important for CD4+ Tcell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs). Mice with hypofunctional GITRL in Lyz2+ cells had decreased LCMV-specific CD4+ Tcell accumulation and increased viral load. GITR signals in CD4+ Tcells occurred after priming to upregulate OX40, CD25, and chemokine receptor CX3CR1. Thus IFN-I (signal 3) induced a post-priming checkpoint (signal 4) for CD4+ Tcell accumulation, revealing a division of labor between cDCs and monocyte-derived APCs in regulating T cell expansion.

Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines

In therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. Since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypes in situ. This review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted and finally question the true meaning of targeting antitumor-based vaccines.

Comparison of microglia and infiltrating CD11c+ cells as antigen presenting cells for T cell proliferation and cytokine response

BackgroundTissue-resident antigen-presenting cells (APC) exert a major influence on the local immune environment. Microglia are resident myeloid cells in the central nervous system (CNS), deriving from early post-embryonic precursors, distinct from adult hematopoietic lineages. Dendritic cells (DC) and macrophages infiltrate the CNS during experimental autoimmune encephalomyelitis (EAE). Microglia are not considered to be as effective APC as DC or macrophages.MethodsIn this work we compared the antigen presenting capacity of CD11c+ and CD11c− microglia subsets with infiltrating CD11c+ APC, which include DC. The microglial subpopulations (CD11c− CD45dim CD11b+ and CD11c+ CD45dim CD11b+) as well as infiltrating CD11c+ CD45high cells were sorted from CNS of C57BL/6 mice with EAE. Sorted cells were characterised by flow cytometry for surface phenotype and by quantitative real-time PCR for cytokine expression. They were co-cultured with primed T cells to measure induction of T cell proliferation and cytokine response.ResultsThe number of CD11c+ microglia cells increased dramatically in EAE. They expressed equivalent levels of major histocompatibility complex and co-stimulatory ligands CD80 and CD86 as those expressed by CD11c+ cells infiltrating from blood. CD11c+ microglia differed significantly from blood-derived CD11c+ cells in their cytokine profile, expressing no detectable IL-6, IL-12 or IL-23, and low levels of IL-1β. By contrast, CD11c− microglia expressed low but detectable levels of all these cytokines. Transforming growth factor β expression was similar in all three populations. Although CNS-resident and blood-derived CD11c+ cells showed equivalent ability to induce proliferation of myelin oligodendrocyte glycoprotein-immunised CD4+ T cells, CD11c+ microglia induced lower levels of T helper (Th)1 and Th17 cytokines, and did not induce Th2 cytokines.ConclusionsOur findings show distinct subtypes of APC in the inflamed CNS, with a hierarchy of functional competence for induction of CD4+ T cell responses.

Histamine Downregulates the Th1-Associated Chemokine IP-10 in Monocytes and Myeloid Dendritic Cells

Background: Histamine is an important mediator of allergic diseases. It modulates the cytokine expression of various subtypes of antigen-presenting cells by four known receptors, H₁R-H₄R. The effects of histamine on myeloid dendritic cells (mDC) are unclear. Methods: Monocytes and mDC were isolated from human PBMC. Histamine receptor expression was evaluated by real-time PCR. Cells were stimulated with histamine and histamine receptor ligands, and restimulated with polyinosinic-polycytidylic acid (poly I:C), and supernatants were analyzed by protein array and ELISA. Results: Monocytes and mDC express H₁R and H₂R without significant differences between the two cell types, whereas H₄R mRNA was significantly higher in mDC compared with monocytes and H₃R mRNA was not detected in any cell type. Prestimulation with histamine caused a significant decrease in poly I:C-induced expression of interferon-γ-induced protein (IP-10) in mDC and monocytes. Stimulation with specific H₁R, H₂R and H₄R agonists and antagonists showed that the observed effect was mediated via H₂R and H₄R in monocytes and mDC. Conclusion: Monocytes and mDC have similar histamine receptor repertoires with regard to H₁R, H₂R and H₃R, but H₄R expression is higher on mDC. Histamine stimulation shows similar functional effects on both cell types, i.e., downregulation of TLR3-induced IP-10 production. This might be a new mechanism how histamine fosters a Th2 milieu.