scholarly journals Local SARS-CoV-2 peptide-specific Immune Responses in Convalescent and Uninfected Human Lung Tissue Models

2021 ◽  
Author(s):  
Kayla F. Goliwas ◽  
Christopher S. Simmons ◽  
Saad A. Khan ◽  
Anthony M. Wood ◽  
Yong Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Lung Tissue ◽  
Human Lung ◽  
Ex Vivo ◽  
T Cell Immunity ◽  
T Cell Subsets ◽  
Human Lung Tissue ◽  
Memory T Cell ◽  
Cell Immunity ◽  
Tissue Models

Multi-specific and long-lasting T cell immunity have been recognized as indicators for long term protection against pathogens including the novel coronavirus SARS-CoV-2, the causative agent of the COVID-19 pandemic. Functional significance of peripheral memory T cell subsets in COVID-19 convalescents (CONV) are beginning to be appreciated; but little is known about lung resident memory T cell (lung TRM) responses and their role in limiting the severity of SARS-CoV-2 infection. Here, we utilize a perfusion three dimensional (3D) human lung tissue model and identify pre-existing local T cell immunity against SARS-CoV-2 spike protein and structural antigens in the lung tissues. We report ex vivo maintenance of functional multi-specific IFN-γ secreting lung TRM in CONV and their induction in lung tissues of vaccinated CONV. Importantly, we identify SARS-CoV-2 spike peptide-responding B cells in lung tissues of CONV in ex vivo 3D-tissue models. Our study highlights a balanced and local anti-viral immune response in the lung and persistent induction of TRM cells as an essential component for future protection against SARS-CoV-2 infection. Further, our data suggest that inclusion of multiple viral antigens in vaccine approaches may broaden the functional profile of memory T cells to combat the severity of coronavirus infection.

scholarly journals A Novel STK4 Mutation Impairs T Cell Immunity Through Dysregulation of Cytokine-Induced Adhesion and Chemotaxis Genes

2021 ◽  
Author(s):  
Andrea Guennoun ◽  
Salim Bougarn ◽  
Taushif Khan ◽  
Rafah Mackeh ◽  
Mahbuba Rahman ◽  
...  
Keyword(s):  
T Cell ◽  
Bacterial Infections ◽  
Genetic Disorder ◽  
Lymphoid Cells ◽  
T Cell Immunity ◽  
T Cell Subsets ◽  
Transcriptional Responses ◽  
Barr Virus ◽  
Cell Immunity ◽  
Gene And Protein Expression

Abstract Purpose Human serine/threonine kinase 4 (STK4) deficiency is a rare, autosomal recessive genetic disorder leading to combined immunodeficiency; however, the extent to which immune signaling and host defense are impaired is unclear. We assessed the functional consequences of a novel, homozygous nonsense STK4 mutation (NM_006282.2:c.871C > T, p.Arg291*) identified in a pediatric patient by comparing his innate and adaptive cell-mediated and humoral immune responses with those of three heterozygous relatives and unrelated controls. Methods The genetic etiology was verified by whole genome and Sanger sequencing. STK4 gene and protein expression was measured by quantitative RT-PCR and immunoblotting, respectively. Cellular abnormalities were assessed by high-throughput RT-RCR, RNA-Seq, ELISA, and flow cytometry. Antibody responses were assessed by ELISA and phage immunoprecipitation-sequencing. Results The patient exhibited partial loss of STK4 expression and complete loss of STK4 function combined with recurrent viral and bacterial infections, notably persistent Epstein–Barr virus viremia and pulmonary tuberculosis. Cellular and molecular analyses revealed abnormal fractions of T cell subsets, plasmacytoid dendritic cells, and NK cells. The transcriptional responses of the patient’s whole blood and PBMC samples indicated dysregulated interferon signaling, impaired T cell immunity, and increased T cell apoptosis as well as impaired regulation of cytokine-induced adhesion and leukocyte chemotaxis genes. Nonetheless, the patient had detectable vaccine-specific antibodies and IgG responses to various pathogens, consistent with a normal CD19 + B cell fraction, albeit with a distinctive antibody repertoire, largely driven by herpes virus antigens. Conclusion Patients with STK4 deficiency can exhibit broad impairment of immune function extending beyond lymphoid cells.

scholarly journals Restored and Enhanced Memory T Cell Immunity in Rheumatoid Arthritis After TNFα Blocker Treatment

2019 ◽  
Vol 10 ◽  
Author(s):  
Asma Khanniche ◽  
Ling Zhou ◽  
Bin Jiang ◽  
Jing Song ◽  
Yanhua Jin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Immunity ◽  
Memory T Cell ◽  
Cell Immunity

scholarly journals Identification and Characterization of CD4+ T Cell Epitopes after Shingrix Vaccination

2020 ◽  
Vol 94 (24) ◽  
Author(s):  
Hannah Voic ◽  
Rory D. de Vries ◽  
John Sidney ◽  
Paul Rubiro ◽  
Erin Moore ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Natural Infection ◽  
Clinical Manifestations ◽  
T Cell Immunity ◽  
Cd4 T Cell ◽  
General Definition ◽  
Elderly Subjects ◽  
Cell Immunity

ABSTRACT Infections with varicella-zoster virus (VZV) are associated with a range of clinical manifestations. Primary infection with VZV causes chicken pox. The virus remains latent in neurons, and it can reactivate later in life, causing herpes zoster (HZ). Two different vaccines have been developed to prevent HZ; one is based on a live attenuated VZV strain (Zostavax), and the other is based on adjuvanted gE recombinant protein (Shingrix). While Zostavax efficacy wanes with age, Shingrix protection retains its efficacy in elderly subjects (individuals 80 years of age and older). In this context, it is of much interest to understand if there is a role for T cell immunity in the differential clinical outcome and if there is a correlate of protection between T cell immunity and Shingrix efficacy. In this study, we characterized the Shingrix-specific ex vivo CD4 T cell responses in the context of natural exposure and HZ vaccination using pools of predicted epitopes. We show that T cell reactivity following natural infection and Zostavax vaccination dominantly targets nonstructural (NS) proteins, while Shingrix vaccination redirects dominant reactivity to target gE. We mapped the gE-specific responses following Shingrix vaccination to 89 different gE epitopes, 34 of which accounted for 80% of the response. Using antigen presentation assays and single HLA molecule-transfected lines, we experimentally determined HLA restrictions for 94 different donor/peptide combinations. Finally, we used our results as a training set to assess strategies to predict restrictions based on measured or predicted HLA binding and the corresponding HLA types of the responding subjects. IMPORTANCE Understanding the T cell profile associated with the protection observed in elderly vaccinees following Shingrix vaccination is relevant to the general definition of correlates of vaccine efficacy. Our study enables these future studies by clarifying the patterns of immunodominance associated with Shingrix vaccination, as opposed to natural infection or Zostavax vaccination. Identification of epitopes recognized by Shingrix-induced CD4 T cells and their associated HLA restrictions enables the generation of tetrameric staining reagents and, more broadly, the capability to characterize the specificity, magnitude, and phenotype of VZV-specific T cells.

scholarly journals Gene transfer to adult human lung tissue ex vivo

Gene Therapy ◽  
2000 ◽  
Vol 7 (8) ◽  
pp. 675-678 ◽  
Author(s):  
S McBride ◽  
D Rannie ◽  
D J Harrison
Keyword(s):  
Gene Transfer ◽  
Lung Tissue ◽  
Human Lung ◽  
Ex Vivo ◽  
Human Lung Tissue ◽  
Adult Human ◽  
Adult Human Lung

scholarly journals Highly selective and rapidly activatable fluorogenic Thrombin sensors and application in human lung tissue

2017 ◽  
Vol 15 (20) ◽  
pp. 4344-4350 ◽  
Author(s):  
Alicia Megia-Fernandez ◽  
Bethany Mills ◽  
Chesney Michels ◽  
Sunay V. Chankeshwara ◽  
Kevin Dhaliwal ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Human Lung ◽  
Ex Vivo ◽  
Human Lung Tissue ◽  
Fluorogenic Probe

A fast and selective fluorogenic probe for Thrombin is reported and applied in ex vivo fibrotic human lung tissue.

scholarly journals A lipidated peptide of Mycobacterium tuberculosis resuscitates the protective efficacy of BCG vaccine by evoking memory T cell immunity

2017 ◽  
Vol 15 (1) ◽  
Author(s):  
Pradeep K. Rai ◽  
Sathi Babu Chodisetti ◽  
Weiguang Zeng ◽  
Sajid Nadeem ◽  
Sudeep K. Maurya ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Protective Efficacy ◽  
T Cell Immunity ◽  
Bcg Vaccine ◽  
Memory T Cell ◽  
Cell Immunity

Segregation of R5 and X4 HIV-1 variants to memory T cell subsets differentially expressing CD62L in ex vivo infected human lymphoid tissue

AIDS ◽  
2002 ◽  
Vol 16 (9) ◽  
pp. 1245-1249 ◽  
Author(s):  
Françoise Gondois-Rey ◽  
Jean-Charles Grivel ◽  
Angelique Biancotto ◽  
Marjorie Pion ◽  
Robert Vigne ◽  
...  
Keyword(s):  
T Cell ◽  
Lymphoid Tissue ◽  
Ex Vivo ◽  
T Cell Subsets ◽  
Memory T Cell ◽  
Human Lymphoid Tissue ◽  
Hiv 1

Measurement of histamine release from human lung tissue ex vivo by microdialysis technique

1998 ◽  
Vol 47 (12) ◽  
pp. 501-505 ◽  
Author(s):  
D. Nissen ◽  
L. J. Petersen ◽  
H. Nolte ◽  
H. Permin ◽  
N. Melchior ◽  
...  
Keyword(s):  
Histamine Release ◽  
Lung Tissue ◽  
Human Lung ◽  
Ex Vivo ◽  
Human Lung Tissue

scholarly journals Children and adults with mild COVID-19 symptoms develop memory T cell immunity to SARS-CoV-2

2021 ◽  
Author(s):  
Patricia Kaaijk ◽  
Veronica Olivo Pimentel ◽  
Maarten E. Emmelot ◽  
Martien Poelen ◽  
Alper Cevirgel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
T Cell Immunity ◽  
Immune Memory ◽  
Effector Memory ◽  
Longitudinal Assessment ◽  
Memory T Cell ◽  
Cell Immunity

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to considerable morbidity/mortality worldwide, but most infections, especially among children, have a mild course. However, it remains largely unknown whether infected children develop cellular immune memory. Methods: To determine whether a memory T cell response is being developed as an indicator for long-term immune protection, we performed a longitudinal assessment of the SARS-CoV-2-specific T cell response by IFN-γ ELISPOT and activation marker expression analyses of peripheral blood samples from children and adults with mild-to-moderate COVID-19. Results: Upon stimulation of PBMCs with heat-inactivated SARS-CoV-2 or overlapping peptides of spike (S-SARS-CoV-2) and nucleocapsid proteins, we found S-SARS-CoV-2-specific IFN-ɣ T cell responses in most infected children (83%) and all adults (100%) that were absent in unexposed controls. Frequencies of SARS-CoV-2-specific T cells were higher in infected adults, especially in those with moderate symptoms, compared to infected children. The S-SARS-CoV-2 IFN-ɣ T cell response correlated with S1-SARS-CoV-2-specific serum IgM, IgG, and IgA antibody concentrations. Predominantly, effector memory CD4+ T cells of a Th1 phenotype were activated upon exposure to SARS-CoV-2 antigens, which persisted for 4-8 weeks after symptom onset. We detected very low frequencies of SARS-CoV-2-reactive CD8+ T cells in these individuals. Conclusions: Our data indicate that an antigen-specific memory CD4+ T cell response is induced in children and adults with mild SARS-CoV-2 infection. T cell immunity induced after mild COVID-19 could contribute to protection against re-infection.

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