Search

The Antarctic krill, Euphausia superba, has evolved seasonal rhythms of physiology and behaviour to survive under the extreme photoperiodic conditions in the Southern Ocean. However, the molecular mechanisms generating these rhythms remain far from understood. The aim of this study was to investigate seasonal differences in gene expression in three different latitudinal regions (South Georgia, South Orkneys/Bransfield Strait, Lazarev Sea) and to identify genes with potential regulatory roles in the seasonal life cycle of Antarctic krill. The RNA-seq data were analysed (a) for seasonal differences between summer and winter krill sampled from each region, and (b) for regional differences within each season. A large majority of genes showed an up-regulation in summer krill in all regions with respect to winter krill. However, seasonal differences in gene expression were less pronounced in Antarctic krill from South Georgia, most likely due to the milder seasonal conditions of the lower latitudes of this region, with a less extreme light regime and food availability between summer and winter. Our results suggest that in the South Orkneys/Bransfield Strait and Lazarev Sea region, Antarctic krill entered a state of metabolic depression and regressed development (winter quiescence) in winter. Moreover, seasonal gene expression signatures seem to be driven by a photoperiodic timing system that may adapt the flexible behaviour and physiology of Antarctic krill to the highly seasonal environment according to the latitudinal region. However, at the lower latitude South Georgia region, food availability might represent the main environmental cue influencing seasonal physiology., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Intranasal infection of mice by Vesicular Stomatitis Virus (VSV) often leads to breakdown of the blood-brain barrier (BBB). The role of Interleukin 12 (IL-12) and nitric oxide synthase (NOS) was examined here. Wild-type (WT), NOS-1 knockout (KO), and NOS-3 KO mice were infected with VSV and treated with either IL-12 or medium. IL-12 treatment of uninfected hosts did not result in pathology. In contrast with WT and NOS-1 KO mice, where extensive gross and ultrastructural correlation of BBB breakdown were evident following infection, in NOS-3 KO mice, integrity of the BBB was observed. Thus NOS-3 activity in astrocytes, endothelial cells, or ependymal cells may play an essential role in regulating the BBB., (Copyright 1999 Academic Press.)

A panel of long-term murine T lymphocyte clones specific for the glycoprotein of vesicular stomatitis virus (VSV) in association with either H-2I-Ad or I-E(d) was tested for the production of cytokines in both resting and poststimulation states using both in situ hybridization and bioassay. All but one of the clones showed antigen-specific cytolytic activity in a 4-hr 51Cr release assay. Unexpectedly, the clones did not appear to be typical Th1 cells. Five of these T cell clones produced both IL-2 and IFN-gamma but not IL-4 after stimulation with either phorbol 12-myristate 13-acetate (PMA) or concanavalin A (Con A). Some clones constitutively expressed mRNA for IL-2 and INF-gamma. The proliferation of these clones was factor independent, suggesting an autocrine growth mechanism. Three clones produced variable levels of IL-4 mRNA and some, to significant quantities, of IL-2 mRNA. One cytolytic clone produced neither IL-2 nor IL-4 mRNA to detectable levels, although mRNA for IFN-gamma was observed. A noncytolytic, Ag-specific clone produced IL-6, tumor necrosis factor (TNF), and lymphotoxin (LT), but no IL-2, IL-4, or IFN-gamma mRNA. There was a strong quantitative correlation between the expression of IL-2-, INF-gamma-, and LT-specific mRNAs by the clones. All the T cell clones tested which secreted INF-gamma and LT expressed no measurable IL-4 mRNA. We examined expression of several other genes in the panel of clones. These included TNF, met-enkephalin (met-enk), IL-1, and IL-6. IL-1 m-RNA synthesis was not observed in any of the T cell clones. Almost all clones produced TNF mRNA. Parallel bioassays showed that secreted IL-2/IL-4 activity levels and mRNA levels correlated well for all clones. Thus, we observed a great degree of heterogeneity among CD4+ cytolytic T lymphocyte clones.

Mechanisms of antigen processing and presentation to thymus-derived lymphocytes have been under intense study for several years, focusing on both Class I-restricted antigen presentation and Class II-MHC restricted responses. The studies described here examine the processing and presentation of exogenously provided soluble glycoprotein of the vesicular stomatitis virus and as well as newly synthesized viral glycoprotein. Evidence is provided that newly synthesized Class II MHC chains are required for cell surface expression of processed glycoprotein determinants irrespective of the origin of the viral antigen. Inhibitors of distinct cellular processes, including ammonium chloride, emetine, and Brefeldin A, have been used to dissect the pathways utilized.

We have studied the interactions of peripheral blood T lymphocytes with cultured human vascular endothelial cells, focusing upon endothelial cell surface antigens important for T cell recognition. Under standard culture conditions endothelial cells express class I but not class II major histocompatibility complex (MHC) antigens. However, class II antigens may be induced by activated T cells or T cell products, including the lymphokine immune interferon. Immune interferon concomitantly increases class I antigen expression and causes a change in cell shape. In addition to vascular endothelial cells, we have found that vascular smooth muscle cells and human dermal fibroblasts may also be induced by immune interferon to express class II antigens. All known human class II antigens are induced (i.e. HLA-DR, DC and SB) as is the associated invariant chain. Induced antigen expression in these cells is stable over several days, although mRNA levels decline rapidly upon withdrawal of interferon. Vascular and stromal cell class II antigens are functional, in that they can be recognized by cytolytic and helper T cell clones. Several non-MHC antigens are also involved in the recognition of endothelial and stromal cells by T cells. We propose a model for the role of inducible class II molecules on endothelium and stromal cells in vivo: The induction of class II MHC antigens on endothelial cells, locally mediated by activated T cells, enables endothelium to present an immunogenic cell surface structure, comprised of antigen plus self class II polymorphic determinants, which in turn, serves to recruit additional antigen-specific T cells from the circulation into the site of a developing cell mediated immune response. Class II molecules on stromal cells, also induced locally at the site of a developing response, confers immune accessory function on these cells and may serve to augment and sustain a T cell response.

Hybrid human-murine major histocompatibility antigens have been constructed and expressed on the surface of both human RD and murine L cell lines after DNA mediated gene transfer. These antigens linked the polymorphic domains (alpha 1 and alpha 2) of H-2Kb and the carboxy-terminal domains (alpha 3, transmembrane, and intracellular) of HLA-A2. Previously we demonstrated that these antigens were serologically intact and were recognized by allospecific cytolytic T lymphocytes. However, the cell lines expressing the hybrid antigen were less well lysed than the native H-2Kb expressing cell lines. In this study, we extend these observations and demonstrate that virally restricted cytolytic T lymphocytes specific for vesicular stomatitis virus and for Sendai virus can recognize cell lines expressing the hybrid antigen, whether expressed on murine (L cell) or human (RD cell) lines. Furthermore, the data show a profound influence by the carboxy-terminal domains upon the polymorphic T-cell restricting epitopes.