γδ T Cell Receptors without a Job

In this issue of Immunity, the studies by Sutton et al. (2009) and Martin et al. (2009) indicate that γδ T cells are innate cells that rapidly produce interleukin (IL)-17 in response to cytokines or pathogens without the need for T cell receptor engagement

Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity

Langerhans cells (LC) form a unique subset of dendritic cells (DC) in the epidermis but so far their in vivo functions in skin immunity and tolerance could not be determined, in particular in relation to dermal DC (dDC). Here, we exploit a novel diphtheria toxin (DT) receptor (DTR)/DT-based system to achieve inducible ablation of LC without affecting the skin environment. Within 24 h after intra-peritoneal injection of DT into Langerin-DTR mice LC are completely depleted from the epidermis and only begin to return 4 wk later. LC deletion occurs by apoptosis in the absence of inflammation and, in particular, the dDC compartment is not affected. In LC-depleted mice contact hypersensitivity (CHS) responses are significantly decreased, although ear swelling still occurs indicating that dDC can mediate CHS when necessary. Our results establish Langerin-DTR mice as a unique tool to study LC function in the steady state and to explore their relative importance compared with dDC in orchestrating skin immunity and tolerance

Beyond the benchtop and the benthos: Dataset management planning and design for time series of ocean carbonate chemistry associated with Durafet (R)-based pH sensors

To better understand the impact of ocean acidification on marine ecosystems, an important ongoing research priority for marine scientists is to characterize present-day pH variability. Following recent technological advances, autonomous pH sensor deployments in shallow coastal marine environments have revealed that pH dynamics in coastal oceans are more variable in space and time than the discrete, open-ocean measurements that are used for ocean acidification projections. Data from these types of deployments will benefit the research community by facilitating the improved design of ocean acidification studies as well as the identification or evaluation of natural and human-influenced pH variability. Importantly, the collection of ecologically relevant pH data and a cohesive, user-friendly integration of results across sites and regions requires (1) effective sensor operation to ensure high quality pH data collection and (2) efficient data management for accessibility and broad reuse by the marine science community. Here, we review the best practices for deployment, calibration, and data processing and quality control, using our experience with Durafet (R)-based pH sensors as a model. Next, we describe information management practices for streamlining preservation and distribution of data and for cataloging different types of pH sensor data, developed in collaboration with two U.S. Long Term Ecological Research (LTER) sites. Finally, we assess sensor performance and data recovery from 73 SeaFET deployments in the Santa Barbara Channel using our quality control guidelines and data management tools, and offer recommendations for improved data yields. Our experience provides a template for other groups contemplating using SeaFET technology as well as general steps that may be helpful for the design of data management for other complex sensors. (C) 2016 The Authors. Published by Elsevier B.V

T-Cell Receptor γδ Bearing Cells in Normal Human Skin

T-cell antigen receptors (TCR) are divided into common αβ and less common γδ types. In the murine skin, TCR γδ+ cells have been reported to form the great majority of epidermal T lymphocytes. We have examined the relative contribution of TCR αβ+ and TCR γδ+ cells to the T-cell population in normal human skin. Serial sections of freshly frozen skin specimens were acetone fixed, incubated with anti-CD3, βF 1 (anti-TCR αβ, anti-TCR γδ-1 and anti-TCR δ1 (anti-TCR γδ) monoclonal antibodies (MoAb), and stained with a highly sensitive method. Over 90% of the T cells of normal human skin are localized around the postcapillary venules of the dermis, while less than 5% are present within the epidermis. In papillary dermis, TCR γδ+ cells formed on average 7% (anti-TCR γδ-1) or 9% (anti-TCR γ1) of the total number of CD3+ cells, while TCR αβ+ cells constituted up to 80%. In epidermis, these percentages were 18% and 29% for TCR γδ+ cells, and up to 60% for TCR γδ+ cells. It is concluded that there is no preferential immigration or in situ expansion of TCR γδ+T cells in normal human skin, because the relative percentages found for the TCR and TCR αβ+ populations in skin are comparable to those found in lymphoid organs and peripheral blood. However, the percentage of TCR γδ+ cells in epidermis seemed on average higher than in papillary dermis. Therefore, there may still be a difference in migration patterns of TCR γδ+ v TCR γβ+ cells, but this does not result in their preferential localization in human epidermis. The hypothesis that TCR γδ+ T cells have a specialized function in immunosurveillance of epithelia may thus not be valid for human epidermis

Complementary Dendritic Cell–activating Function of CD8+ and CD4+ T Cells: Helper Role of CD8+ T Cells in the Development of T Helper Type 1 Responses

Dendritic cells (DCs) activated by CD40L-expressing CD4+ T cells act as mediators of “T helper (Th)” signals for CD8+ T lymphocytes, inducing their cytotoxic function and supporting their long-term activity. Here, we show that the optimal activation of DCs, their ability to produce high levels of bioactive interleukin (IL)-12p70 and to induce Th1-type CD4+ T cells, is supported by the complementary DC-activating signals from both CD4+ and CD8+ T cells. Cord blood– or peripheral blood–isolated naive CD8+ T cells do not express CD40L, but, in contrast to naive CD4+ T cells, they are efficient producers of IFN-γ at the earliest stages of the interaction with DCs. Naive CD8+ T cells cooperate with CD40L-expressing naive CD4+ T cells in the induction of IL-12p70 in DCs, promoting the development of primary Th1-type CD4+ T cell responses. Moreover, the recognition of major histocompatibility complex class I–presented epitopes by antigen-specific CD8+ T cells results in the TNF-α– and IFN-γ–dependent increase in the activation level of DCs and in the induction of type-1 polarized mature DCs capable of producing high levels of IL-12p70 upon a subsequent CD40 ligation. The ability of class I–restricted CD8+ T cells to coactivate and polarize DCs may support the induction of Th1-type responses against class I–presented epitopes of intracellular pathogens and contact allergens, and may have therapeutical implications in cancer and chronic infections

On the lateral fluid motion during pool boiling via preferentially located cavities

Passively generated lateral motion of fluid during pool boiling on asymmetrically textured mesoscale structures is discussed in this Letter. The surface texture is in the form of 30°–60° mm-scale ratchets with re-entrant cavities located on the 30° face. High speed visualization of growing bubbles from cavities indicates growth and departure normal to the 30° face of the ratchets. A semi-empirical model of net axial liquid velocity due to the non-vertical bubble growth is developed and validated in a pool boiling experiment

Th1 Lymphokine Production Profiles of Nickel-Specific CD4+ T-Lymphocyte Clones from Nickel Contact Allergic and Non-Allergic Individuals

Panels of nickel-specific T-lymphocyte clones (TLC) were prepared from nickel-allergic and non-allergic donors. TLC from both panels showed similar levels of expression of TCRα/β, CD4, CD2, CD25, and CD29 and recognized nickel in association with class II HLA molecules with restriction determinants in HLA-DR, HLA-DP, and HLA-DQ. The lymphokine secretion was analyzed in TLC from both panels upon antigen-specific or non-specific stimulation and was compared with the secretion profiles of representants of pre-established human atopen-specific Th1 and Th2 cells. Nickel-specific TLC from both panels showed a lymphokine secretion pattern similar to the atopen-specific Th1 cells, although there was some variation from clone to clone. Most TLC secreted substantial amounts of IFN-γ, IL-2, TNF-α and GM-CSF, but little or no IL-4 and IL-5. The variation observed mainly concerned IL-2 secretion that could be low or absent in some of the TLC. The general secretion pattern did not change upon different modes of stimulation, including activation via CD3, CD2, or CD28. Because nickel-specific TLC from allergic and non-allergic individuals show a similar Th1 secretion pattern, the present results give no evidence that aberrant lymphokine secretion by CD4+ T cells determines the contact allergic state, as was found for atopic allergy in a previous study

Helicobacter pylori Modulates the T Helper Cell 1/T Helper Cell 2 Balance through Phase-variable Interaction between Lipopolysaccharide and DC-SIGN

The human gastric pathogen Helicobacter pylori spontaneously switches lipopolysaccharide (LPS) Lewis (Le) antigens on and off (phase-variable expression), but the biological significance of this is unclear. Here, we report that Le+ H. pylori variants are able to bind to the C-type lectin DC-SIGN and present on gastric dendritic cells (DCs), and demonstrate that this interaction blocks T helper cell (Th)1 development. In contrast, Le− variants escape binding to DCs and induce a strong Th1 cell response. In addition, in gastric biopsies challenged ex vivo with Le+ variants that bind DC-SIGN, interleukin 6 production is decreased, indicative of increased immune suppression. Our data indicate a role for LPS phase variation and Le antigen expression by H. pylori in suppressing immune responses through DC-SIGN

Identification of a unique intervillous cellular signature in chronic histiocytic intervillositis

Introduction: Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta characterized by an infiltrate of CD68+ cells in the intervillous space. CHI is associated with adverse pregnancy outcomes such as miscarriage, fetal growth restriction, and (late) intrauterine fetal death. The adverse pregnancy outcomes and a variable recurrence rate of 25-100% underline its clinical relevance. The pathophysiologic mechanism of CHI is unclear, but it appears to be immunologically driven. The aim of this study was to obtain a better understanding of the phenotype of the cellular infiltrate in CHI.Method: We used imaging mass cytometry to achieve in-depth visualization of the intervillous maternal immune cells and investigated their spatial orientation in situ in relation to the fetal syncytiotrophoblast.Results: We found three phenotypically distinct CD68+HLA-DR+CD38+ cell clusters that were unique for CHI. Additionally, syncytiotrophoblast cells in the vicinity of these CD68+HLA-DR+CD38+ cells showed decreased expression of the immunosuppressive enzyme CD39.Discussion: The current results provide novel insight into the phenotype of CD68+ cells in CHI. The identification of unique CD68+ cell clusters will allow more detailed analysis of their function and could result in novel therapeutic targets for CHI.Research into fetal development and medicin