NKT cells and CD8+ T cells are dispensable for T cell dependent allergic airway inflammation

2007 ◽  
Author(s):  
Jyoti Das ◽  
Paul Eynott ◽  
Luc Van Kaer ◽  
Yufang Shi ◽  
Gobardhan Das
Keyword(s):  
T Cells ◽  
T Cell ◽  
Airway Inflammation ◽  
Cd8 T Cells ◽  
Allergic Airway Inflammation ◽  
Nkt Cells

Natural killer T cells and CD8+ T cells are dispensable for T cell–dependent allergic airway inflammation

2006 ◽  
Vol 12 (12) ◽  
pp. 1345-1346 ◽  
Author(s):  
Jyoti Das ◽  
Paul Eynott ◽  
Ray Jupp ◽  
Alfred Bothwell ◽  
Luc Van Kaer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Airway Inflammation ◽  
Natural Killer ◽  
Cd8 T Cells ◽  
Allergic Airway Inflammation ◽  
Natural Killer T Cells ◽  
Killer T Cells ◽  
Natural Killer T

scholarly journals Bystander suppression of allergic airway inflammation by lung resident memory CD8+ T cells

2004 ◽  
Vol 101 (16) ◽  
pp. 6116-6121 ◽  
Author(s):  
B. J. Marsland ◽  
N. L. Harris ◽  
M. Camberis ◽  
M. Kopf ◽  
S. M. Hook ◽  
...  
Keyword(s):  
T Cells ◽  
Airway Inflammation ◽  
Cd8 T Cells ◽  
Allergic Airway Inflammation ◽  
Memory Cd8 T Cells ◽  
Bystander Suppression

scholarly journals Natural Killer T Cell Ligand α-Galactosylceramide Enhances Protective Immunity Induced by Malaria Vaccines

2002 ◽  
Vol 195 (5) ◽  
pp. 617-624 ◽  
Author(s):  
Gloria Gonzalez-Aseguinolaza ◽  
Luc Van Kaer ◽  
Cornelia C. Bergmann ◽  
James M. Wilson ◽  
John Schmieg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Viral Infections ◽  
Tumor Development ◽  
Nkt Cells ◽  
Cell Mediated Immunity ◽  
Natural Killer T

The important role played by CD8+ T lymphocytes in the control of parasitic and viral infections, as well as tumor development, has raised the need for the development of adjuvants capable of enhancing cell-mediated immunity. It is well established that protective immunity against liver stages of malaria parasites is primarily mediated by CD8+ T cells in mice. Activation of natural killer T (NKT) cells by the glycolipid ligand, α-galactosylceramide (α-GalCer), causes bystander activation of NK, B, CD4+, and CD8+ T cells. Our study shows that coadministration of α-GalCer with suboptimal doses of irradiated sporozoites or recombinant viruses expressing a malaria antigen greatly enhances the level of protective anti-malaria immunity in mice. We also show that coadministration of α-GalCer with various different immunogens strongly enhances antigen-specific CD8+ T cell responses, and to a lesser degree, Th1-type responses. The adjuvant effects of α-GalCer require CD1d molecules, Vα14 NKT cells, and interferon γ. As α-GalCer stimulates both human and murine NKT cells, these findings should contribute to the design of more effective vaccines against malaria and other intracellular pathogens, as well as tumors.

scholarly journals Essential role of Notch signaling in effector memory CD8+ T cell–mediated airway hyperresponsiveness and inflammation

2008 ◽  
Vol 205 (5) ◽  
pp. 1087-1097 ◽  
Author(s):  
Masakazu Okamoto ◽  
Katsuyuki Takeda ◽  
Anthony Joetham ◽  
Hiroshi Ohnishi ◽  
Hiroyuki Matsuda ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Notch Signaling ◽  
Airway Inflammation ◽  
Cd8 T Cells ◽  
Adoptive Transfer ◽  
Airway Hyperresponsiveness ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Notch Ligand

Adoptive transfer of in vivo–primed CD8+ T cells or in vitro–generated effector memory CD8+ T (TEFF) cells restores airway hyperresponsiveness (AHR) and airway inflammation in CD8-deficient (CD8−/−) mice. Examining transcription levels, there was a strong induction of Notch1 in TEFF cells compared with central memory CD8+ T cells. Treatment of TEFF cells with a γ-secretase inhibitor (GSI) strongly inhibited Notch signaling in these cells, and after adoptive transfer, GSI-treated TEFF cells failed to restore AHR and airway inflammation in sensitized and challenged recipient CD8−/− mice, or to enhance these responses in recipient wild-type (WT) mice. These effects of GSI were also associated with increased expression of the Notch ligand Delta1 in TEFF cells. Treatment of sensitized and challenged WT mice with Delta1-Fc resulted in decreased AHR and airway inflammation accompanied by higher levels of interferon γ in bronchoalveolar lavage fluid. These results demonstrate a role for Notch in skewing the T cell response from a T helper (Th)2 to a Th1 phenotype as a consequence of the inhibition of Notch receptor activation and the up-regulation of the Notch ligand Delta1. These data are the first to show a functional role for Notch in the challenge phase of CD8+ T cell–mediated development of AHR and airway inflammation, and identify Delta1 as an important regulator of allergic airway inflammation.

scholarly journals RhoA and Cdc42 in T cells: Are they targetable for T cell-mediated inflammatory diseases?

2021 ◽  
Author(s):  
Fukun Guo
Keyword(s):  
T Cells ◽  
T Cell ◽  
Airway Inflammation ◽  
Inflammatory Diseases ◽  
Gene Knockout ◽  
Allergic Airway Inflammation ◽  
Cell Types ◽  
Small Gtpases ◽  
Cellular Functions ◽  
Biological Targets

Abstract Many inflammatory diseases are not curable, necessitating a better understanding of their pathobiology that may help identify novel biological targets. RhoA and Cdc42 of Rho family small GTPases regulate a variety of cellular functions such as actin cytoskeletal organization, cell adhesion, migration, proliferation, and survival. Recent characterization of mouse models of conditional gene knockout of RhoA and Cdc42 has revealed their physiological and cell type-specific roles in a number of cell types. In T lymphocytes, which play an important role in the pathogenesis of most, if not all, of the inflammatory diseases, we and others have investigated the effects of T cell-specific knockout of RhoA and Cdc42 on T cell development in the thymus, peripheral T cell homeostasis, activation, and differentiation to effector and regulatory T cells, and on T cell-mediated allergic airway inflammation and colitis. Here we highlight the phenotypes resulting from RhoA and Cdc42 deletion in T cells and discuss whether pharmacological targeting of RhoA and Cdc42 is feasible in treating asthma that is driven by allergic airway inflammation and colitis.

scholarly journals BpOmpW Antigen Stimulates the Necessary Immune Correlates of Protection Against Melioidosis

2021 ◽  
Author(s):  
Julen Tomas-Cortazar ◽  
Siobhan McClean
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Nkt Cells ◽  
Control Group ◽  
Insulin Resistant ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Hla Dq

Melioidosis is a fatal disease caused by Burkholderia pseudomallei Gram-negative bacteria. It is the causative of 89,000 deaths per year in endemic areas of Southeast Asia and Northern Australia. Diabetes mellitus is the most risk factor, increasing 12-fold the susceptibility for severe disease. IFN-y responses from CD4 and CD8 T cells, but also from NK and NKT cells are necessary to eliminate the pathogen. Elucidating the immune correlates of protection of our previously described protective BpOmpW vaccine is an essential step of any vaccine before clinical trials. Thus, we immunized non-insulin resistant C57BL/6j mice and an insulin resistant C57BL/6j mouse model of Type 2 Diabetes (T2D) with BpOmpW using Sigma Adjuvant System (SAS) (treatment) or SAS only (control). Two weeks later bloods and spleens were collected and serological analysis & in vitro exposure of splenocytes to the antigen for 60 hours were performed in both controls and treatment groups to finally analyze the stained splenocytes by flow cytometry. BpOmpW induced strong antibody response, stimulated effector CD4+ and CD8+ T cells and CD4+ CD25+ Foxp3+regulatory T cells and produced higher IFN-y; responses in CD4+, CD8+, NK and NKT cells relative to the control group in non-insulin resistant mice. T cell responses of insulin resistant mice to BpOmpW were comparable to those in non-insulin resistant mice. In addition, as a precursor to its evaluation in human studies, humanised HLA-DR and HLA-DQ transgenic mice elicited IFN-y; recall responses in an ELISPoT-based study and PBMCs from donors that were in contact to BpOmpW for seven days experienced T cell proliferation. Finally, plasma from melioidosis survivors with diabetes recognized our BpOmpW vaccine antigen. Overall, these range of approaches used strongly indicate that BpOmpW elicits the required immune correlates of protection to combat melioidosis and bring the vaccine closer to clinical trials.

scholarly journals PRMT5 in T cells drives Th17 responses, mixed granulocytic inflammation and severe allergic airway inflammation

2021 ◽  
Author(s):  
Brandon W Lewis ◽  
Stephanie A Amici ◽  
Hye-Young Kim ◽  
Emily Shalosky ◽  
Aiman Khan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Airway Inflammation ◽  
Severe Asthma ◽  
Lung Inflammation ◽  
Airway Remodeling ◽  
Symptom Control ◽  
Hospital Costs ◽  
Allergic Airway Inflammation ◽  
Arginine Methylation

Severe asthma is characterized by steroid insensitivity and poor symptom control, and is responsible for the majority of asthma-related hospital costs. Therapeutic options remain limited, in part due to a lack of mechanisms driving severe asthma phenotypes. Increased arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is increased in asthmatic lungs. Here, we show that PRMT5 drives allergic airway inflammation in a mouse model reproducing multiple aspects of human severe asthma. We find that PRMT5 is required in CD4+ T cells for chronic steroid-insensitive severe lung inflammation, with selective T cell deletion of PRMT5 robustly suppressing eosinophilic and granulocytic lung inflammation, pathology, airway remodeling and hyperresponsiveness. Mechanistically, we observed high pulmonary sterol metabolic activity, ROR-γt and Th17 responses, with PRMT5-dependent increases in ROR-γt agonist desmosterol. Our work demonstrates that T cell PRMT5 drives severe allergic lung inflammation and has potential implications for the pathogenesis and therapeutic targeting of severe asthma.

scholarly journals Interactions between NKT cells and Tregs are required for tolerance to combined bone marrow and organ transplants

Blood ◽  
2012 ◽  
Vol 119 (6) ◽  
pp. 1581-1589 ◽  
Author(s):  
David Hongo ◽  
Xiaobin Tang ◽  
Suparna Dutt ◽  
Roland G. Nador ◽  
Samuel Strober
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Conditioning Regimen ◽  
Nkt Cells ◽  
T Cell Subsets ◽  
Lymphoid Tissues ◽  
Dependent Manner ◽  
Cell Production

Abstract We used a model of combined bone marrow and heart transplantation, in which tolerance and stable chimerism is induced after conditioning with fractionated irradiation of the lymphoid tissues and anti–T-cell antibodies. Graft acceptance and chimerism required host CD4+CD25+ Treg production of IL-10 that was in-turn enhanced by host invariant natural killer (NK) T-cell production of IL-4. Up-regulation of PD-1 on host Tregs, CD4+CD25− conventional T (Tcon) cells, and CD8+ T cells was also enhanced by NKT cell production of IL-4. Up-regulated PD-1 expression on Tregs was linked to IL-10 secretion, on CD8+ T cells was linked to Tim-3 expression, and on CD4+ Tcon cells was associated with reduced IFNγ secretion. Changes in the expression of PD-1 were induced by the conditioning regimen, and declined after bone marrow transplantation. In conclusion, NKT cells in this model promoted changes in expression of negative costimulatory receptors and anti-inflammatory cytokines by Tregs and other T-cell subsets in an IL-4–dependent manner that resulted in tolerance to the bone marrow and organ grafts.

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