Ageing enhances cellular immunity to myeloperoxidase and experimental anti-myeloperoxidase glomerulonephritis

Rheumatology ◽  
2021 ◽  
Author(s):  
Maliha A Alikhan ◽  
Juli Jaw ◽  
Lani R Shochet ◽  
Kate J Robson ◽  
Joshua D Ooi ◽  
...  
Keyword(s):  
Cellular Immunity ◽  
Interferon Γ ◽  
T Cell Epitopes ◽  
Small Blood Vessel ◽  
Aged Mice ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Anca Associated Vasculitis ◽  
Interleukin 17A ◽  
Passive Antibody Transfer

Abstract Objectives Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disease characterised by small blood vessel inflammation, commonly affecting the kidneys and respiratory tract. It is unclear why the incidence of this condition increases with age. Previous studies in a passive antibody transfer system in aged mice have implicated innate effectors. To test the hypothesis that autoimmunity to myeloperoxidase, an autoantigen responsible for ANCA-associated vasculitis, increases with age, anti-myeloperoxidase autoimmunity was studied in murine models of active autoimmunity and disease induced by cellular immunity. Methods Young (8 weeks) and aged (either 15 or 22 month) mice were immunised with whole proteins or peptides from ovalbumin, as a model foreign antigen, or myeloperoxidase protein or peptides. Mice were subjected to a model of active anti-myeloperoxidase glomerulonephritis. Cellular and humoral immune responses and tissue inflammation were assessed. Results While cellular immunity to ovalbumin was diminished in aged mice, cellular autoimmunity to myeloperoxidase and its immunodominant CD4+ and CD8+ T cell epitopes was increased after immunization with either MPO peptides or whole MPO protein, assessed by peptide and antigen specific production of the pro-inflammatory cytokines interferon-γ and interleukin-17A. MPO-ANCA titres were not increased in aged mice compared with young mice. In experimental anti-MPO glomerulonephritis, cell mediated injury was increased, likely due to CD4+ and CD8+ T cells, innate immunity and the increased vulnerability of aged kidneys. Conclusion Heightened cellular immunity to MPO develops with ageing in mice and may contribute to the increased incidence and severity of ANCA-associated vasculitis in older people.

Control of Cellular and Humoral Immune Responses by Peptides Containing T-cell Epitopes

1989 ◽  
Vol 54 (0) ◽  
pp. 497-504 ◽  
Author(s):  
M.T. Scherer ◽  
B.M.C. Chan ◽  
F. Ria ◽  
J.A. Smith ◽  
D.L. Perkins ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Epitopes ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Imbalance of Circulatory T Follicular Helper and T Follicular Regulatory Cells in Patients with ANCA-Associated Vasculitis

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Ying Xu ◽  
Hongmei Xu ◽  
Yu Zhen ◽  
Xueting Sang ◽  
Hao Wu ◽  
...  
Keyword(s):  
Immunosuppressive Treatment ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Healthy Controls ◽  
Regulatory Cells ◽  
Humoral Immune ◽  
Tfh Cells ◽  
Humoral Immune Responses ◽  
Follicular Helper ◽  
Anca Associated Vasculitis ◽  
Kidney Involvement

Antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV) is characterized by small-vessel inflammation in association with autoantibodies. Balance between T follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells is critical for humoral immune responses. Accumulating evidence supports that Tfh and Tfr are involved in autoimmune diseases; however, their roles in AAV are unclear. In this study, we tested the changes of circulatory Tfh and Tfr in patients with AAV. Twenty patients with AAV and twenty healthy controls were enrolled. Sixteen AAV patients had kidney involvement. We found that the AAV patients had increased circulating Tfh cells (CD4+CXCR5+CD25−CD127interm-hi), decreased Tfr cells (CD4+CXCR5+CD25+CD127lo-interm), and elevated Tfh/Tfr ratios compared with healthy controls (P<0.01). The Tfh percentage and Tfh/Tfr ratio, but not Tfr percentage, were positively correlated to proteinuria levels and BVAS scores in patients with AAV (P<0.01). In addition, AAV patients had decreased circulating Tfh1 (CCR6-CXCR3+), but increased Tfh2 cells (CCR6-CXCR3-), compared with healthy controls (P<0.01), indicating a Tfh1-to-Tfh2 shift. Furthermore, remission achieved by immunosuppressive treatment markedly attenuated the increase of total Tfh (P<0.01) and Tfh2 cells (P<0.05), promoted the Tfh1 response (P<0.05), and recovered the balance between Tfh/Tfr cells (P<0.05) and between Tfh1/Tfh2 cells (P<0.05) in patients with AAV. Plasma levels of IL-21, a cytokine secreted by Tfh cells, were elevated in AAV patients compared with healthy controls (P<0.01), which was attenuated by immunosuppressive treatment (P<0.05). Taken together, our findings indicate that circulatory Tfh/Tfr ratios, Tfh2/Tfh1 shift, and plasma IL-21 levels are associated with AAV and disease activity.

The novel adjuvant IC31® strongly improves influenza vaccine-specific cellular and humoral immune responses in young adult and aged mice

Vaccine ◽  
2008 ◽  
Vol 26 (27-28) ◽  
pp. 3461-3468 ◽  
Author(s):  
Karin Riedl ◽  
Rosemarie Riedl ◽  
Alexander von Gabain ◽  
Eszter Nagy ◽  
Karen Lingnau
Keyword(s):  
Young Adult ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
The Novel ◽  
Aged Mice ◽  
Humoral Immune ◽  
Humoral Immune Responses

A New Method for Screening Natural Products to Stimulate IFN-γ Production in Jurkat Human T Lymphocytes

2020 ◽  
Vol 26 (1) ◽  
pp. 130-139
Author(s):  
Yan Ouyang ◽  
Xiaoming Zhong ◽  
Hongqun Liao ◽  
Pengcheng Zhu ◽  
Kaiyuan Luo ◽  
...  
Keyword(s):  
Natural Products ◽  
Interferon Γ ◽  
Jurkat Cells ◽  
High Content Screening ◽  
Dependent Manner ◽  
Activated T Cells ◽  
Humoral Immune ◽  
Screening Model ◽  
Humoral Immune Responses ◽  
Ifn Γ

Interferon-γ (IFN-γ) is a critical cytokine in the defense against viral and bacterial infection. It is mainly produced by natural killer cells and activated T cells. Given its regulatory role in coordinating cellular and humoral immune responses, IFN-γ is considered to be an effective therapeutic agent in the treatment of viral infection. Here we established a fluorescence-based high-content screening model to find small molecules that can stimulate the production of IFN-γ in human Jurkat cells. After a primary screening of 267 natural products, two hits, Astragalus polyphenols and 6-shogaol, were identified to promote the activity of the IFN-γ promoter and subsequently validated by the flow cytometry assay. Obviously, both Astragalus polyphenols and 6-shogaol exhibited potential to induce the transcription and expression of IFN-γ in a dose-dependent manner. These results indicated that our high-content screening model could be a credible and useful platform to contribute to the discovery of novel molecules to promote the expression of IFN-γ and provide leading compounds for the treatment of viral infectious diseases.

scholarly journals Induction of T Helper Type 1 and 2 Responses to 19-Kilodalton Merozoite Surface Protein 1 in Vaccinated Healthy Volunteers and Adults Naturally Exposed to Malaria

2002 ◽  
Vol 70 (3) ◽  
pp. 1417-1421 ◽  
Author(s):  
Edwin A. M. Lee ◽  
Dupeh R. Palmer ◽  
Katie L. Flanagan ◽  
William H. H. Reece ◽  
Kennedy Odhiambo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Interleukin 4 ◽  
T Cell Epitopes ◽  
Humoral Immune ◽  
Merozoite Surface Protein 1 ◽  
Humoral Immune Responses ◽  
Human Volunteers ◽  
The Tropics

ABSTRACT Plasmodium falciparum malaria is a major cause of death in the tropics. The 19-kDa subunit of P. falciparum merozoite surface protein 1 (MSP-119), a major blood stage vaccine candidate, is the target of cellular and humoral immune responses in animals and humans. In this phase I trial of MSP-119, immunization of nonexposed human volunteers with either of the two allelic forms of recombinant MSP-119 induced high levels of antigen-specific Th1 (gamma interferon) and Th2 (interleukin 4 [IL-4] and IL-10) type lymphokines. The adjustment of the antigen dose and number of immunizations regulated the level of specificity of immune responses and Th1/Th2 bias of responses induced by vaccination. Novel conserved and allelic T-cell epitopes which induced cross-strain immune responses were identified. Importantly, responses to many of these novel epitopes were also present in adults exposed to malaria, both in east (Kenya) and west Africa (The Gambia). These data suggest that epitope-specific naturally acquired MSP-119 immune responses in endemic populations can be boosted by vaccination.

scholarly journals Cellular and humoral immunogenicity of a SARS-CoV-2 mRNA vaccine in patients on hemodialysis

2021 ◽  
Author(s):  
Monika Strengert ◽  
Matthias Becker ◽  
Gema Morilla Ramos ◽  
Alex Dulovic ◽  
Jens Gruber ◽  
...  
Keyword(s):  
At Risk ◽  
Immune Responses ◽  
Binding Capacity ◽  
Interferon Γ ◽  
Intermittent Hemodialysis ◽  
Humoral Immune ◽  
Vaccine Responses ◽  
Humoral Immune Responses ◽  
Increased Risk ◽  
Cellular Immune

Abstract Background Patients with chronic renal insufficiency on intermittent hemodialysis face an increased risk of COVID-19 induced mortality and impaired vaccine responses. To date, only few studies addressed SARS-CoV-2 vaccine elicited immunity in this immunocompromised population. Methods We assessed immunogenicity of the mRNA vaccine BNT162b2 in at risk dialysis patients and characterized systemic cellular and humoral immune responses in serum and saliva using interferon γ release assay and multiplex-based cytokine and immunoglobulin measurements. We further compared binding capacity and neutralization efficacy of vaccination-induced immunoglobulins against emerging SARS-CoV-2 variants of concern B.1.1.7, B.1.351, B.1.429 and Cluster 5 by ACE2-RBD competition assay. Findings Patients on intermittent hemodialysis exhibit detectable but variable cellular and humoral immune responses against SARS-CoV-2 and variants of concern after a two-dose regimen of BNT162b2. Although vaccination-induced immunoglobulins were detectable in saliva and plasma, both anti-SARS-CoV-2 IgG and neutralization efficacy was reduced compared to controls. Similarly, T-cell mediated interferon γ release after stimulation with SARS-CoV-2 spike peptides was significantly diminished. Interpretation Quantifiable humoral and cellular immune responses after BNT162b2 vaccination in individuals on intermittent dialysis are encouraging, but urge for longitudinal follow-up to assess longevity of immunity. Diminished virus neutralization and interferon γ responses in face of emerging variants of concern may favor this at risk population for re-vaccination using modified vaccines at the earliest opportunity.

scholarly journals Polystyrene nanoparticles induce stronger cellular and more durable humoral immune responses against an inactivated bovine herpesvirus 1 isolate

2020 ◽  
Author(s):  
Xingbo Liu ◽  
Zhihao Xin ◽  
Fan Zhang ◽  
Luyao zhang ◽  
Hanyu Yan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Bovine Herpesvirus ◽  
Interferon Γ ◽  
Antibody Responses ◽  
Live Virus ◽  
Herpesvirus Type ◽  
Humoral Immune ◽  
Development Platform ◽  
Humoral Immune Responses

Abstract The inactivated bovine herpesvirus type 1(BoHV-1) vaccines are generally safe and suitable for use in dairy and pregnant cattle, but induces weaker cellular immune responses and shorter antibody responses compared with the modified live virus vaccine. In this study, we used polystyrene (PS) nanoparticles (100 nm) as a carrier for purified inactivated broken BoHV-1 to improve cellular and humoral immune responses compared with the traditional inactivated vaccine. Mice were injected intramuscularly with the inactivated complex mixed with ISA206 adjuvant. Transmission electron microscopy showed that the PS nanoparticles displayed broken BoHV-1 on their surfaces. After validation of BoHV-1 and gB gC gD gE tegument proteins, it proved that the BoHV-conjugated PS nanoparticles induced higher-titer and more durable antibody responses. The inactivated BoHV-PS nanoparticle complex elicited neutralizing antibodies (titer ~2 6 ) in 5 weeks post-immunization in mice. The CD4/CD8 ratio was higher in mice immunized with PS nanoparticles compared with other groups. However, this ratio reached its maximum 1 week later than in mice immunized with ISA206+BoHV-1 or BoHV-1. Levels of interleukin (IL)-4, IL-6, and interferon-γ in followed similar patterns. In conclusion, this pilot study demonstrated that PS nanoparticles can adjuvant inactivated BoHV-1 vaccines, enhancing both cell-mediated immune responses and the duration of antibody responses. This study provides the foundation for a new development platform for inactivated vaccines, which can elicit potent cellular and humoral immune responses in animals and humans.The inactivated bovine herpesvirus type 1(BoHV-1) vaccines are generally safe and suitable for use in dairy and pregnant cattle, but induces weaker cellular immune responses and shorter antibody responses compared with the modified live virus vaccine. In this study, we used polystyrene (PS) nanoparticles (100 nm) as a carrier for purified inactivated broken BoHV-1 to improve cellular and humoral immune responses compared with the traditional inactivated vaccine. Mice were injected intramuscularly with the inactivated complex mixed with ISA206 adjuvant. Transmission electron microscopy showed that the PS nanoparticles displayed broken BoHV-1 on their surfaces. After validation of BoHV-1 and gB gC gD gE tegument proteins, it proved that the BoHV-conjugated PS nanoparticles induced higher-titer and more durable antibody responses. The inactivated BoHV-PS nanoparticle complex elicited neutralizing antibodies (titer ~2 6 ) in 5 weeks post-immunization in mice. The CD4/CD8 ratio was higher in mice immunized with PS nanoparticles compared with other groups. However, this ratio reached its maximum 1 week later than in mice immunized with ISA206+BoHV-1 or BoHV-1. Levels of interleukin (IL)-4, IL-6, and interferon-γ in followed similar patterns. In conclusion, this pilot study demonstrated that PS nanoparticles can adjuvant inactivated BoHV-1 vaccines, enhancing both cell-mediated immune responses and the duration of antibody responses. This study provides the foundation for a new development platform for inactivated vaccines, which can elicit potent cellular and humoral immune responses in animals and humans.

scholarly journals Evaluation of Cellular Immunity with ASFV Infection by Swine Leukocyte Antigen (SLA)—Peptide Tetramers

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2264
Author(s):  
Wenqiang Sun ◽  
He Zhang ◽  
Wenhui Fan ◽  
Lihong He ◽  
Teng Chen ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Cellular Immunity ◽  
African Swine Fever Virus ◽  
Economic Losses ◽  
Cell Immune Response ◽  
Swine Leukocyte Antigen ◽  
Leukocyte Antigen ◽  
Humoral Immune ◽  
Humoral Immune Responses

African swine fever virus (ASFV) causes acute hemorrhagic fever in domestic pigs and wild boars, resulting in incalculable economic losses to the pig industry. As the mechanism of viral infection is not clear, protective antigens have not been discovered or identified. In this study, we determined that the p30, pp62, p72, and CD2v proteins were all involved in the T cell immune response of live pigs infected with ASFV, among which p72 and pp62 proteins were the strongest. Panoramic scanning was performed on T cell epitopes of the p72 protein, and three high-frequency positive epitopes were selected to construct a swine leukocyte antigen (SLA)-tetramer, and ASFV-specific T cells were detected. Subsequently, the specific T cell and humoral immune responses of ASFV-infected pigs and surviving pigs were compared. The results demonstrate that the specific T cellular immunity responses gradually increased during the infection and were higher than that in the surviving pigs in the late stages of infection. The same trend was observed in specific humoral immune responses, which were highest in surviving pigs. In general, our study provides key information for the exploration of ASFV-specific immune responses and the development of an ASFV vaccine.

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