Search results for "killer"

High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glyc…

2021

Upon infection withMycobacterium tuberculosis(Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lip…

Angiotensin II-induced vascular dysfunction depends on interferon-γ-driven immune cell recruitment and mutual activation of monocytes and NK-cells.

2013

Objective— Immune cells contribute to angiotensin II (ATII)–induced vascular dysfunction and inflammation. Interferon-γ (IFN-γ), an inflammatory cytokine exclusively produced by immune cells, seems to be involved in ATII-driven cardiovascular injury, but the actions and cellular source of IFN-γ remain incompletely understood. Approach and Results— IFN-γ −/− and Tbx21 −/− mice were partially protected from ATII-induced (1 mg/kg per day of ATII, infused subcutaneously by miniosmotic pumps) vascular endothelial and smooth muscle dysfunction, whereas mice overexpressing IFN-γ showed constitutive vascular dysfunction. Absence of T-box expressed in T cells (T-bet), the IFN-γ transcription factor…

Relationship of curative surgery on natural killer cell activity in colorectal cancer.

1996

Aim of this study has been to evaluate natural killer (NK) activity in patients with colorectal tumors before and after curative surgery.Forty colorectal cancer patients without distant metastases were stratified according to American Joint Committee on Cancer/International Union Against Cancer staging system into three categories: Stage I (n = 12), Stage II (n = 15), and Stage III (n = 13). All of them underwent curative resection, and there were no major postoperative complications. Venous blood samples were obtained preoperatively, at surgical wound closure, and on the 1st, 7th, and 21st postoperative days. Mononuclear cells were isolated over Ficoll-Hypaque (Lymphoprep, Nycomed Pharma A…

The Shwartzman reaction repealed

2007

The article, “ -Galactosylceramide induces protection against lipopolysaccharide-induced shock” (doi:10.1189/jlb.0506298), was selected as a Pivotal Advance because the results suggest that -galactosylceramide ( GalCer), a glycolipid isolated from marine sponges, can protect against the complete morbidity and mortality characterisitic of endotoxin shock by inducing NKT cells to produce TH2 cytokines.

T cells in reactive arthritis

1993

T cells appear to play a major role in the development, maintenance and also resolution of reactive arthritis (ReA). Recent advances in understanding the processes involved in T cell activation now allow us to examine the peripheral blood and synovial fluid T cell responses to given "arthritogenic" microorganisms in terms of antigen specificity, epitope identification, cytokine secretion patterns, HLA restriction and the role of different T cell subsets in ReA. Peripheral blood bulk proliferation and limiting dilution studies provide evidence that the peripheral T cell response against arthritis-associated gram-negative bacteria is decreased in patients developing immunological sequelae suc…

Conformational control of Bax localization and apoptotic activity by Pro168.

2004

In healthy cells, Bax resides inactive in the cytosol because its COOH-terminal transmembrane region (TMB) is tucked into a hydrophobic pocket. During apoptosis, Bax undergoes a conformational change involving NH2-terminal exposure and translocates to mitochondria to release apoptogenic factors. How this process is regulated remains unknown. We show that the TMB of Bax is both necessary and sufficient for mitochondrial targeting. However, its availability for targeting depends on Pro168 located within the preceding loop region. Pro168 mutants of Bax lack apoptotic activity, cannot rescue the apoptosis-resistant phenotype of Bax/Bak double knockout cells, and are retained in the cytosol even…

The NFκB-inducing kinase is essential for the developmental programming of skin-resident and IL-17-producing γδ T cells

2015

γδ T cells contribute to first line immune defense, particularly through their ability for rapid production of proinflammatory cytokines. The cytokine profile of γδ T cells is hard-wired already during thymic development. Yet, the molecular pathways underlying this phenomenon are incompletely understood. Here we show that signaling via the NFκB-inducing kinase (NIK) is essential for the formation of a fully functional γδ T cell compartment. In the absence of NIK, development of Vγ5+ dendritic epidermal T cells (DETCs) was halted in the embryonic thymus, and impaired NIK function caused a selective loss of IL-17 expression by γδ T cells. Using a novel conditional mutant of NIK, we could show…

2014

The maturation status of dendritic cells determines whether interacting T cells are activated or if they become tolerant. Previously we could induce T cell tolerance by applying a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor (HMGCRI) atorvastatin, which also modulates MHC class II expression and has therapeutic potential in autoimmune disease. Here, we aimed at elucidating the impact of this therapeutic strategy on T cell differentiation as a consequence of alterations in dendritic cell function. We investigated the effect of HMGCRI during differentiation of peripheral human monocytes and murine bone marrow precursors to immature DC in vitro and assessed their phenotype. To …

The Putative Natural Killer Decoy Early Genem04(gp34) of Murine Cytomegalovirus Encodes an Antigenic Peptide Recognized by Protective Antiviral CD8 T…

2000

ABSTRACTSeveral early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation to cytolytic T lymphocytes (CTL). Specifically, them152gene product gp37/40 causes retention of MHC-I molecules in the endoplasmic reticulum (ER)-Golgi intermediate compartment. Lack of MHC-I on the cell surface should activate natural killer (NK) cells recognizing the “missing self.” The retention, however, is counteracted by them04early gene product gp34, which binds to folded MHC-I molecules in the ER and directs the complex to the cell surface. It was thus speculated that gp34 mi…

The Immune Evasion Paradox: Immunoevasins of Murine Cytomegalovirus Enhance Priming of CD8 T Cells by Preventing Negative Feedback Regulation▿

2008

ABSTRACTCytomegaloviruses express glycoproteins that interfere with antigen presentation to CD8 T cells. Although the molecular modes of action of these “immunoevasins” differ between cytomegalovirus species, the convergent biological outcome is an inhibition of the recognition of infected cells. In murine cytomegalovirus, m152/gp40 retains peptide-loaded major histocompatibility complex class I molecules in acis-Golgi compartment, m06/gp48 mediates their vesicular sorting for lysosomal degradation, and m04/gp34, although not an immunoevasin in its own right, appears to assist in the concerted action of all three molecules. Using the Ld-restricted IE1 epitope YPHFMPTNL in the BALB/c mouse m…