Imaging mass cytometry is a technology that enables comprehensive analysis of cellular phenotypes at the tissue level. We performed a multiparameter characterization of structural and immune cell populations in psoriatic skin and synovial tissue samples aimed at characterizing immune cell differences in patients with psoriasis and psoriatic arthritis. A panel of 33 antibodies was used to stain selected immune and structural cell populations.
View Article and Find Full Text PDFJ Invest Dermatol
September 2021
Typically found in the skin, Candida albicans can be both commensal and pathogen. In their report, Zhang et al. (2021) address the regulation of C.
View Article and Find Full Text PDFVaricella zoster virus, the worldwide infectious human virus responsible for acute varicella and chickenpox, commonly spreads from exposure through contact with a skin lesion or airborne respiratory droplets. Keratinocytes, major targets and source of transmission of the virus present in the skin, represent an ideal choice of cell to stop early virus progression. In their recent study, Tommasi et al.
View Article and Find Full Text PDFDendritic cells (DCs) are one of the earliest targets of HIV-1 infection acting as a "Trojan horse," concealing the virus from the innate immune system and delivering it to T cells via virological synapses (VS). To explicate how the virus is trafficked through the cell to the VS and evades degradation, a high-throughput small interfering RNA screen targeting membrane trafficking proteins was performed in monocyte-derived DCs. We identified several proteins including BIN-1 and RAB7L1 that share common roles in transport from endosomal compartments.
View Article and Find Full Text PDFHuman T-cell leukemia virus type 1 (HTLV-1) propagates within and between individuals via cell-to-cell transmission, and primary infection typically occurs across juxtaposed mucosal surfaces during breastfeeding or sexual intercourse. It is therefore likely that dendritic cells (DCs) are among the first potential targets for HTLV-1. However, it remains unclear how DCs contribute to virus transmission and dissemination in the early stages of infection.
View Article and Find Full Text PDFLangerhans cells (LCs) are likely among the first targets of HIV-1 infection due to their localization in mucosal tissues. In their recent work, Pena-Cruz and colleagues were able to study HIV-1 infection in vaginal epithelial DCs (VEDCs), termed CD1a+ VEDCs. They show that VEDCs are distinct from other blood- and tissue-derived DCs or LCs because they express the protein langerin but not the lectin receptor DC-SIGN, and they do not have Birbeck granules.
View Article and Find Full Text PDFThymic stromal lymphopoietin (TSLP) and IL-7 are related cytokines that mediate growth and differentiation events in the immune system. They signal through IL-7Rα-containing receptors. Target cells of TSLP in Th2 responses include CD4 T cells and dendritic cells (DCs).
View Article and Find Full Text PDFThe chemokine receptor, CXC chemokine receptor 4 (CXCR4), is selective for CXC chemokine ligand 12 (CXCL12), is broadly expressed in blood and tissue cells, and is essential during embryogenesis and hematopoiesis. CXCL14 is a homeostatic chemokine with unknown receptor selectivity and preferential expression in peripheral tissues. Here, we demonstrate that CXCL14 synergized with CXCL12 in the induction of chemokine responses in primary human lymphoid cells and cell lines that express CXCR4.
View Article and Find Full Text PDFCutaneous vaccination can be a challenge because the development of local skin inflammation is often unavoidable. Thus, it is important to identify and validate new vaccine adjuvants that enhance immunization without the burden of inflammation. Wang et al.
View Article and Find Full Text PDFInfections caused by bacteria in the airway preferentially induce a Th17 response. However, the mechanisms involved in the regulation of CD4 T-cell responses in the lungs are incompletely understood. Here, we have investigated the mechanisms involved in the regulation of Th17 differentiation in the lungs in response to immunization with lipopolysaccharide (LPS) as an adjuvant.
View Article and Find Full Text PDFDelivery of vaccine formulations into the dermis using antigen-coated microneedle patches is a promising and safe approach because of efficient antigen delivery and safety. We evaluated an intradermal vaccine using HIV-1 p24 Gag peptide-conjugated polypropylene sulfide nanoparticles to induce immunity against HIV-1. This peptide-conjugated polypropylene sulfide nanoparticle formulation did not accelerate the maturation of blood- or skin-derived subsets of dendritic cells, either generated in vitro or purified ex vivo, despite efficient uptake in the absence of adjuvant.
View Article and Find Full Text PDFPurpose Of Review: The purpose of this study is to describe the alterations that HIV-1 induces in antigen-presenting cells (APCs), in vitro, ex vivo and in vivo.
Recent Findings: HIV-1 disarms several arms of the immune system including APCs. We summarize here recent findings on the impact of the virus on APC.
Screening a complete mouse phosphatase lentiviral shRNA library using high-throughput sequencing revealed several phosphatases that regulate CD4 T-cell differentiation. We concentrated on two lipid phosphatases, the myotubularin-related protein (MTMR)9 and -7. Silencing MTMR9 by shRNA or siRNA resulted in enhanced T-helper (Th)1 differentiation and increased Th1 protein kinase B (PKB)/AKT phosphorylation while silencing MTMR7 caused increased Th2 and Th17 differentiation and increased AKT phosphorylation in these cells.
View Article and Find Full Text PDFHere, we show that interleukin-1 (IL-1) enhances antigen-driven CD8 T cell responses. When administered to recipients of OT-I T cell receptor transgenic CD8 T cells specific for an ovalbumin (OVA) peptide, IL-1 results in an increase in the numbers of wild-type but not IL1R1(-/-) OT-I cells, particularly in spleen, liver, and lung, upon immunization with OVA and lipopolysaccharide. IL-1 administration also results in an enhancement in the frequency of antigen-specific cells that are granzyme B(+), have cytotoxic activity, and/ or produce interferon γ (IFN-γ).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2013
The proportion of CD4 T cells with phenotypic and functional properties of naïve cells out of total CD4 T cells is similar in the lung parenchyma and lymph nodes. On treatment with a sphingosine-1-phosphate agonist, the frequency of these cells falls precipitously, but with a delay of ∼14 h compared with blood CD4 T cells; neither anti-CD62L nor pertussis toxin prevents entry of naïve CD4 T cells into the lung. Based on treatment with anti-CD62L and the use of CCR7(-/-) cells, lung naïve CD4 T cells appear to migrate to the mediastinal lymph nodes along a CD62L-independent, CCR7-dependent pathway.
View Article and Find Full Text PDFMemory phenotype (CD44(bright), CD25(negative)) CD4 spleen and lymph node T cells (MP cells) proliferate rapidly in normal or germ-free donors, with BrdU uptake rates of 6% to 10% per day and Ki-67 positivity of 18% to 35%. The rapid proliferation of MP cells stands in contrast to the much slower proliferation of lymphocytic choriomeningitis virus (LCMV)-specific memory cells that divide at rates ranging from <1% to 2% per day over the period from 15 to 60 days after LCMV infection. Anti-MHC class II antibodies fail to inhibit the in situ proliferation of MP cells, implying a non-T-cell receptor (TCR)-driven proliferation.
View Article and Find Full Text PDFIL-1 strikingly enhances antigen-driven responses of CD4 and CD8 T cells. It is substantially more effective than LPS and when added to a priming regime of antigen plus LPS, it strikingly enhances cell expansion. The effect is mediated by direct action on CD4 and CD8 T cells; the response occurs when OT-I or OT-II cells are transferred to B6 IL-1R1-/- recipients and only cells that express IL-1 receptors can respond.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2011
Antigen-driven expansion of specific CD4 T cells diminishes, on a per cell basis, as infused cell number increases. There is a linear relation between log precursor number and log factor of expansion (FE), with a slope of ∼-0.5 over a range from 3 to 30,000 precursors.
View Article and Find Full Text PDFThe mechanisms underlying tolerance to noninherited maternal Ags (NIMA) are not fully understood. In this study, we designed a double-transgenic model in which all the offspring's CD8(+) T cells corresponded to a single clone recognizing the K(b) MHC class I protein. In contrast, the mother and the father of the offspring differed by the expression of a single Ag, K(b), that served as NIMA.
View Article and Find Full Text PDFWe have studied the mechanisms of tolerance induction to self-MHC antigens in mouse B cells during fetal development and the post-natal period. To monitor the fate of autoreactive B cell clones, we used the 3-83 micro delta B cell receptor (BCR)-transgenic (Tg) and -knock-in (KI) mouse models. These BCR-Tg and -KI B cells recognize the MHC class I molecules H-2K(k) and H-2K(b), with a high or moderate affinity, respectively.
View Article and Find Full Text PDFCD25(+) regulatory T cells (Treg) are a heterogeneous population that exists as CD44(low) and CD44(high) cells. Here we report that while both CD44(low) and CD44(high) Treg are anergic and express similar levels of Foxp3, CD44(high) Treg are highly proliferative in vivo and are more potent suppressors in vitro than CD44(low) Treg. From analysis of the properties of Treg derived from germ-free mice, it was concluded that peptide antigens derived from intestinal microorganisms are not essential for the generation, in vivo proliferation or suppressive activity of Treg.
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