scholarly journals Healthy but not RSV-infected lung epithelial cells profoundly inhibit T cell activation

Thorax ◽  
2009 ◽  
Vol 64 (4) ◽  
pp. 283-290 ◽  
Author(s):  
H Wang ◽  
Z Su ◽  
J Schwarze
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lung Epithelial Cells ◽  
Lung Epithelial

scholarly journals SARS-CoV-2 Spike 1 Protein Controls Natural Killer Cell Activation via the HLA-E/NKG2A Pathway

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1975 ◽  
Author(s):  
Daria Bortolotti ◽  
Valentina Gentili ◽  
Sabrina Rizzo ◽  
Antonella Rotola ◽  
Roberta Rizzo
Keyword(s):  
Epithelial Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Activation ◽  
Nk Cell ◽  
Killer Cell ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Spike Proteins

Natural killer cells are important in the control of viral infections. However, the role of NK cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has previously not been identified. Peripheral blood NK cells from SARS-CoV and SARS-CoV-2 naïve subjects were evaluated for their activation, degranulation, and interferon-gamma expression in the presence of SARS-CoV and SARS-CoV-2 spike proteins. K562 and lung epithelial cells were transfected with spike proteins and co-cultured with NK cells. The analysis was performed by flow cytometry and immune fluorescence. SARS-CoV and SARS-CoV-2 spike proteins did not alter NK cell activation in a K562 in vitro model. On the contrary, SARS-CoV-2 spike 1 protein (SP1) intracellular expression by lung epithelial cells resulted in NK cell-reduced degranulation. Further experiments revealed a concomitant induction of HLA-E expression on the surface of lung epithelial cells and the recognition of an SP1-derived HLA-E-binding peptide. Simultaneously, there was increased modulation of the inhibitory receptor NKG2A/CD94 on NK cells when SP1 was expressed in lung epithelial cells. We ruled out the GATA3 transcription factor as being responsible for HLA-E increased levels and HLA-E/NKG2A interaction as implicated in NK cell exhaustion. We show for the first time that NK cells are affected by SP1 expression in lung epithelial cells via HLA-E/NKG2A interaction. The resulting NK cells’ exhaustion might contribute to immunopathogenesis in SARS-CoV-2 infection.

scholarly journals S1713 Autophagy in Colitis: T Cell Activation Induces Autophagy in Crypt Epithelial Cells in GFP-LC3 Mice

2010 ◽  
Vol 138 (5) ◽  
pp. S-259
Author(s):  
Neha V Patel ◽  
David Ivancic ◽  
Ramanarao Dirisina ◽  
Rebecca B. Katzman ◽  
Terrence A. Barrett
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
T Cell Activation ◽  
Cell Activation

Pneumococci induced TLR- and Rac1-dependent NF-κB-recruitment to the IL-8 promoter in lung epithelial cells

2006 ◽  
Vol 290 (4) ◽  
pp. L730-L737 ◽  
Author(s):  
Bernd Schmeck ◽  
Sylvia Huber ◽  
Kerstin Moog ◽  
Janine Zahlten ◽  
Andreas C. Hocke ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Activation ◽  
Rho Gtpase ◽  
Dominant Negative ◽  
Lung Epithelial Cells ◽  
Dominant Negative Mutant ◽  
Epithelial Cell Line ◽  
Phosphatidylinositol 3 Kinase ◽  
Lung Epithelial ◽  
Phosphatidylinositol 3

Streptococcus pneumoniae is the major pathogen of community-acquired pneumonia. The respiratory epithelium constitutes the first line of defense against invading lung pathogens, including pneumococci. We analyzed the involvement of Toll-like receptors (TLR) and Rho-GTPase signaling in the activation of human lung epithelial cells by pneumococci. S. pneumoniae induced release of interleukin-8 (IL-8) by human bronchial epithelial cell line BEAS-2B. Specific inhibition of Rac1 by Nsc23766 or a dominant-negative mutant of Rac1 strongly reduced cytokine release. In addition, pneumococci-related cell activation (IL-8 release, NF-κB-activation) depended on MyD88, phosphatidylinositol 3-kinase, and Cdc42 but not on RhoA. Pneumococci enhanced TLR1 and TLR2 mRNA expression in BEAS-2B cells, whereas TLR4 and TLR6 expression was constitutively high. TLR1 and 2 synergistically recognized pneumococci in cotransfection experiments. TLR4, TLR6, LPS-binding protein, and CD14 seem not to be involved in pneumococci-dependent cell activation. At the IL-8 gene promoter, recruitment of phosphorylated NF-κB subunit p65 was blocked by inhibition of Rac1, whereas binding of the phosphorylated activator protein-1 subunit c-Jun to the promoter was not diminished. In summary, these results suggest that S. pneumoniae activate human epithelial cells by TLR1/2 and a phosphatidylinositol 3-kinase- and Rac1-dependent NF-κB-recruitment to the IL-8 promoter.

scholarly journals Human intestinal epithelial cell-induced CD8+ T cell activation is mediated through CD8 and the activation of CD8-associated p56lck.

1995 ◽  
Vol 182 (4) ◽  
pp. 1079-1088 ◽  
Author(s):  
Y Li ◽  
X Y Yio ◽  
L Mayer
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Intestinal Epithelial Cells ◽  
T Cell Proliferation ◽  
Intestinal Epithelial

The activation of CD8+ suppressor T cells by normal intestinal epithelial cells in antigen-specific or allogeneic mixed cell culture systems has significant implications for the regulation of mucosal immune responses. In this study, we found that the capacity of epithelial cells to induce CD8+ suppressor T cell activation appeared to be linked to the binding of CD8 molecules on the T cell surface. This appears to be mediated by a non-class I molecule expressed on the epithelial cell surface, which binds to CD8 and results in the activation of the CD8-associated src-like tyrosine kinase, p56lck. Epithelial cell-stimulated p56lck activation is an early event (in contrast to monocytes) and is essential for T cell activation, since proliferation could be completely abrogated by pretreatment of T cells with genestein or herbamycin, both of which are protein tyrosine kinase inhibitors. Pretreatment of T cells with anti-CD8 or of intestinal epithelial cells with an anti-epithelial cell mAb B9 inhibited p56lck activation and further confirmed that CD8 on the T cell and a CD8 ligand on the epithelial cell were involved in this T cell activation event. The specificity of this reaction was confirmed in experiments in which murine transfectants 3G4 and 3G8, expressing CD4 or CD8, respectively, were used. Coculture of 3G8 with epithelial cells but not with monocytes activated p56lck in this cell line, whereas p56lck was preferentially activated in 3G4 cells when monocytes were used as the stimulator cells. Although stimulation through CD8- and CD8-associated p56lck was important for epithelial cell-induced T cell activation, T cell proliferation could not be induced by cross-linking CD8 alone with monoclonal antibody anti-CD8. These data suggest that a second signal, possibly through the T cell antigen receptor since activation of the T cell receptor-associated kinase fyn was also seen, is required for epithelial cell-driven T cell proliferation.

scholarly journals Sars-Cov-2 Spike 1 protein control Natural killer cells activation via HLA-E/NKG2A pathway.

2020 ◽  
Author(s):  
Daria Bortolotti ◽  
Valentina Gentili ◽  
Sabrina Rizzo ◽  
Antonella Rotola ◽  
Roberta Rizzo
Keyword(s):  
Epithelial Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Activation ◽  
Viral Infections ◽  
Nk Cell ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Spike Proteins

Abstract Natural killer (NK) cells are important in the control of viral infections. However, the role of NK cells during Sars-Cov-2 infection has previously not been identified. Peripheral blood NK cells from Sars-Cov and Sars-Cov-2 naïve subjects were evaluated for their activation, degranulation, interferon-gamma expression in the presence of Sars-Cov and Sars-Cov-2 spike proteins. K562 and lung epithelial cells were transfected with spike proteins and co-cultured with NK cells. The analysis was performed by flow cytometry and immune-fluorescence. Sars-Cov and Sars-Cov-2 spike proteins did not alter NK cell activation in K562 in vitro model. On the contrary, Sars-Cov-2 spike 1 protein (SP1) intracellular expression by lung epithelial cells resulted in NK cell reduced degranulation. Further experiments revealed a concomitant induction of HLA-E expression on the surface of lung epithelial cells and the recognition of a SP1-derived HLA-E-binding peptide. Simultaneously, there was the up-modulation of the inhibitory receptor NKG2A/CD94 on NK cells when SP1 is expressed in lung epithelial cells. We ruled out GATA3 transcription factor as responsible for HLA-E increased levels and HLA-E/NKG2A interaction as implicate in NK cells exhaustion. We show for the first time that NK cells are affected by SP1 expression in lung epithelial cells via HLA-E/NKG2A interaction. The resulting NK cells exhaustion might contribute to immunopathogenesis in Sars-Cov-2 infection.

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