Immune Responses in Laying Hens after an Infectious Bronchitis Vaccination of Pullets: A Comparison of Two Vaccination Strategies

For decades, vaccinations have been used to limit infectious bronchitis (IB) in both the broiler and layer industries. Depending on the geographical area, live attenuated vaccines are used either alone or in combination with inactivated vaccines to control infectious bronchitis virus (IBV) infections. It has been shown that administering inactivated vaccines preceded by priming with live attenuated vaccines in pullets protects laying hens against IB. However, the immunological basis of this protective response has not been adequately investigated. The objective of the study was to compare two vaccination strategies adapted by the Canadian poultry industry in terms of their ability to systemically induce an adequate immune response in IBV-impacted tissues in laying hens. The first vaccination strategy (only live attenuated IB vaccines) and second vaccination strategy (live attenuated and inactivated IB vaccines) were applied. Serum anti-IBV antibodies were measured at two time points, i.e., 3 weeks and 10 weeks post last vaccination. The recruitment of T cell subsets (i.e., CD4+ and CD8+ T cells), and the interferon (IFN)-γ mRNA expression were measured at 10 weeks post last vaccination. We observed that vaccination strategy 2 induced significantly higher serum anti-IBV antibody responses that were capable of neutralizing an IBV Mass variant associated with a flock history of shell-less egg production better than a Delmarva (DMV)1639 variant, as well as a significantly higher IFN-γ mRNA expression in the lungs, kidneys, and oviduct. We also observed that both vaccination strategies recruited CD4+ T cells as well as CD8+ T cells to the examined tissues at various extents. Our findings indicate that vaccination strategy 2 induces better systemic and local host responses in laying hens.

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Early Response of CD8+ T Cells in COVID-19 Patients

Journal of Personalized Medicine ◽

10.3390/jpm11121291 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1291

Author(s):

Deni Ramljak ◽

Martina Vukoja ◽

Marina Curlin ◽

Katarina Vukojevic ◽

Maja Barbaric ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

T Cells ◽

Mrna Expression ◽

Cd8 T Cells ◽

Expression Profiles ◽

Expression Patterns ◽

Effector Memory ◽

Healthy Controls ◽

Ifn Γ

Healthy and controlled immune response in COVID-19 is crucial for mild forms of the disease. Although CD8+ T cells play important role in this response, there is still a lack of studies showing the gene expression profiles in those cells at the beginning of the disease as potential predictors of more severe forms after the first week. We investigated a proportion of different subpopulations of CD8+ T cells and their gene expression patterns for cytotoxic proteins (perforin-1 (PRF1), granulysin (GNLY), granzyme B (GZMB), granzyme A (GZMA), granzyme K (GZMK)), cytokine interferon-γ (IFN-γ), and apoptotic protein Fas ligand (FASL) in CD8+ T cells from peripheral blood in first weeks of SARS-CoV-2 infection. Sixteen COVID-19 patients and nine healthy controls were included. The absolute counts of total lymphocytes (p = 0.007), CD3+ (p = 0.05), and CD8+ T cells (p = 0.01) in COVID-19 patients were significantly decreased compared to healthy controls. In COVID-19 patients in CD8+ T cell compartment, we observed lower frequency effector memory 1 (EM1) (p = 0.06) and effector memory 4 (EM4) (p < 0.001) CD8+ T cells. Higher mRNA expression of PRF1 (p = 0.05) and lower mRNA expression of FASL (p = 0.05) at the fifth day of the disease were found in COVID-19 patients compared to healthy controls. mRNA expression of PRF1 (p < 0.001) and IFN-γ (p < 0.001) was significantly downregulated in the first week of disease in COVID-19 patients who progressed to moderate and severe forms after the first week, compared to patients with mild symptoms during the entire disease course. GZMK (p < 0.01) and FASL (p < 0.01) mRNA expression was downregulated in all COVID-19 patients compared to healthy controls. Our results can lead to a better understanding of the inappropriate immune response of CD8+ T cells in SARS-CoV2 with the faster progression of the disease.

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Nitric Oxide is Involved in the Upregulation of IFN-γ and IL-10 mRNA Expression by CD8+ T Cells During the Blood Stages of P. chabaudi AS Infection in CBA/Ca Mice

International Journal of Biological Sciences ◽

10.7150/ijbs.7.1401 ◽

2011 ◽

Vol 7 (9) ◽

pp. 1401-1411 ◽

Cited By ~ 11

Author(s):

M Legorreta-Herrera ◽

S Rivas-Contreras ◽

JL Ventura-Gallegos ◽

A Zentella-Dehesa

Keyword(s):

Nitric Oxide ◽

T Cells ◽

Mrna Expression ◽

Cd8 T Cells ◽

Ifn Γ

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CD4+CD25- effector T cells from healthy controls and MS patients do not differ in mRNA expression of IFN-γ, IL-2, and TNF-α

Aktuelle Neurologie ◽

10.1055/s-2004-833325 ◽

2004 ◽

Vol 31 (S 1) ◽

Author(s):

A Hug ◽

J Haas ◽

A Viehöver ◽

B Fritz ◽

B Storch-Hagenlocher ◽

...

Keyword(s):

T Cells ◽

Mrna Expression ◽

Effector T Cells ◽

Healthy Controls ◽

Tnf Α ◽

Ifn Γ

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Phase 1 study of safety, tolerability and immunogenicity of the human telomerase (hTERT)-encoded DNA plasmids INO-1400 and INO-1401 with or without IL-12 DNA plasmid INO-9012 in adult patients with solid tumors

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-003019 ◽

2021 ◽

Vol 9 (7) ◽

pp. e003019

Author(s):

Robert H Vonderheide ◽

Kimberly A Kraynyak ◽

Anthony F Shields ◽

Autumn J McRee ◽

Jennifer M Johnson ◽

...

Keyword(s):

Pancreatic Cancer ◽

T Cells ◽

Cd8 T Cells ◽

Plasmid Dna ◽

Phase 1 ◽

Dna Encoding ◽

Cancer Types ◽

Ifn Γ ◽

Human Telomerase ◽

Disease Free

BackgroundHuman telomerase reverse transcriptase (hTERT) is frequently classified as a ‘universal’ tumor associated antigen due to its expression in a vast number of cancers. We evaluated plasmid DNA-encoded hTERT as an immunotherapy across nine cancer types.MethodsA phase 1 clinical trial was conducted in adult patients with no evidence of disease following definitive surgery and standard therapy, who were at high risk of relapse. Plasmid DNA encoding one of two hTERT variants (INO-1400 or INO-1401) with or without plasmid DNA encoding interleukin 12 (IL-12) (INO-9012) was delivered intramuscularly concurrent with the application of the CELLECTRA constant-current electroporation device 4 times across 12 weeks. Safety assessments and immune monitoring against native (germline, non-mutated, non-plasmid matched) hTERT antigen were performed. The largest cohort of patients enrolled had pancreatic cancer, allowing for additional targeted assessments for this tumor type.ResultsOf the 93 enrolled patients who received at least one dose, 88 had at least one adverse event; the majority were grade 1 or 2, related to injection site. At 18 months, 54.8% (51/93) patients were disease-free, with median disease-free survival (DFS) not reached by end of study. For patients with pancreatic cancer, the median DFS was 9 months, with 41.4% of these patients remaining disease-free at 18 months. hTERT immunotherapy induced a de novo cellular immune response or enhanced pre-existing cellular responses to native hTERT in 96% (88/92) of patients with various cancer types. Treatment with INO-1400/INO-1401±INO-9012 drove hTERT-specific IFN-γ production, generated hTERT-specific CD4+ and CD8+ T cells expressing the activation marker CD38, and induced hTERT-specific activated CD8 +CTLs as defined by cells expressing perforin and granzymes. The addition of plasmid IL-12 adjuvant elicited higher magnitudes of cellular responses including IFN-γ production, activated CD4+ and CD8+ T cells, and activated CD8+CTLs. In a subset analysis of pancreatic cancer patients, the presence of immunotherapy-induced activated CD8+ T cells expressing PD-1, granzymes and perforin correlated with survival.ConclusionsPlasmid DNA-encoded hTERT/IL-12 DNA immunotherapy was well-tolerated, immune responses were noted across all tumor types, and a specific CD8+ phenotype increased by the immunotherapy was significantly correlated with survival in patients with pancreatic cancer.

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CD8 T Cells Use IFN-γ To Protect against the Lethal Effects of a Respiratory Poxvirus Infection

The Journal of Immunology ◽

10.4049/jimmunol.1400256 ◽

2014 ◽

Vol 192 (11) ◽

pp. 5415-5425 ◽

Cited By ~ 21

Author(s):

John Goulding ◽

Georges Abboud ◽

Vikas Tahiliani ◽

Pritesh Desai ◽

Tarun E. Hutchinson ◽

...

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Lethal Effects ◽

Ifn Γ

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Vaccination with DNA Encoding the Immunodominant LACK Parasite Antigen Confers Protective Immunity to Mice Infected with Leishmania major

Journal of Experimental Medicine ◽

10.1084/jem.186.7.1137 ◽

1997 ◽

Vol 186 (7) ◽

pp. 1137-1147 ◽

Cited By ~ 255

Author(s):

Sanjay Gurunathan ◽

David L. Sacks ◽

Daniel R. Brown ◽

Steven L. Reiner ◽

Hughes Charest ◽

...

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Protective Immunity ◽

Leishmania Major ◽

Protective Efficacy ◽

Dna Vaccination ◽

Attractive Alternative ◽

Dna Immunization ◽

Dna Encoding ◽

Ifn Γ

To determine whether DNA immunization could elicit protective immunity to Leishmania major in susceptible BALB/c mice, cDNA for the cloned Leishmania antigen LACK was inserted into a euykaryotic expression vector downstream to the cytomegalovirus promoter. Susceptible BALB/c mice were then vaccinated subcutaneously with LACK DNA and challenged with L. major promastigotes. We compared the protective efficacy of LACK DNA vaccination with that of recombinant LACK protein in the presence or absence of recombinant interleukin (rIL)-12 protein. Protection induced by LACK DNA was similar to that achieved by LACK protein and rIL-12, but superior to LACK protein without rIL-12. The immunity conferred by LACK DNA was durable insofar as mice challenged 5 wk after vaccination were still protected, and the infection was controlled for at least 20 wk after challenge. In addition, the ability of mice to control infection at sites distant to the site of vaccination suggests that systemic protection was achieved by LACK DNA vaccination. The control of disease progression and parasitic burden in mice vaccinated with LACK DNA was associated with enhancement of antigen-specific interferon-γ (IFN-γ) production. Moreover, both the enhancement of IFN-γ production and the protective immune response induced by LACK DNA vaccination was IL-12 dependent. Unexpectedly, depletion of CD8+ T cells at the time of vaccination or infection also abolished the protective response induced by LACK DNA vaccination, suggesting a role for CD8+ T cells in DNA vaccine induced protection to L. major. Thus, DNA immunization may offer an attractive alternative vaccination strategy against intracellular pathogens, as compared with conventional vaccination with antigens combined with adjuvants.

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NKG2D+ IFN-γ+ CD8+ T Cells Are Responsible for Palladium Allergy

PLoS ONE ◽

10.1371/journal.pone.0086810 ◽

2014 ◽

Vol 9 (2) ◽

pp. e86810 ◽

Cited By ~ 13

Author(s):

Mitsuko Kawano ◽

Masafumi Nakayama ◽

Yusuke Aoshima ◽

Kyohei Nakamura ◽

Mizuho Ono ◽

...

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Ifn Γ

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Virally Activated CD8 T Cells Home to Mycobacterium bovis BCG-Induced Granulomas but Enhance Antimycobacterial Protection Only in Immunodeficient Mice

Infection and Immunity ◽

10.1128/iai.00943-06 ◽

2006 ◽

Vol 75 (3) ◽

pp. 1154-1166 ◽

Cited By ~ 10

Author(s):

Laura H. Hogan ◽

Dominic O. Co ◽

Jozsef Karman ◽

Erika Heninger ◽

M. Suresh ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Mycobacterium Bovis ◽

Cd8 T Cells ◽

Bacterial Load ◽

Granulomatous Inflammation ◽

Cd8 T Cell ◽

Activated T Cells ◽

Immunodeficient Mice ◽

Ifn Γ

ABSTRACT The effect of secondary infections on CD4 T-cell-regulated chronic granulomatous inflammation is not well understood. Here, we have investigated the effect of an acute viral infection on the cellular composition and bacterial protection in Mycobacterium bovis strain bacille Calmette-Guérin (BCG)-induced granulomas using an immunocompetent and a partially immunodeficient murine model. Acute lymphocytic choriomeningitis virus (LCMV) coinfection of C57BL/6 mice led to substantial accumulation of gamma interferon (IFN-γ)-producing LCMV-specific T cells in liver granulomas and increased local IFN-γ. Despite traffic of activated T cells that resulted in a CD8 T-cell-dominated granuloma, the BCG liver organ load was unaltered from control levels. In OT-1 T-cell-receptor (TCR) transgenic mice, ovalbumin (OVA) immunization or LCMV coinfection of BCG-infected mice induced CD8 T-cell-dominated granulomas containing large numbers of non-BCG-specific activated T cells. The higher baseline BCG organ load in this CD8 TCR transgenic animal allowed us to demonstrate that OVA immunization and LCMV coinfection increased anti-BCG protection. The bacterial load remained substantially higher than in mice with a more complete TCR repertoire. Overall, the present study suggests that peripherally activated CD8 T cells can be recruited to chronic inflammatory sites, but their contribution to protective immunity is limited to conditions of underlying immunodeficiency.

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