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2022 ◽  
Author(s):  
Braxton L. Jamison ◽  
James E. DiLisio ◽  
K. Scott Beard ◽  
Tobias Neef ◽  
Brenda Bradley ◽  
...  

The induction of antigen (Ag)-specific tolerance and replacement of islet β-cells are major ongoing goals for the treatment of Type 1 Diabetes (T1D). Our group previously showed that a hybrid insulin peptide (2.5HIP) is a critical autoantigen for diabetogenic CD4<sup>+</sup> T cells in the non-obese diabetic (NOD) mouse model. In this study, we investigated whether induction of Ag-specific tolerance using 2.5HIP-coupled tolerogenic nanoparticles (NPs) could protect diabetic NOD mice from disease recurrence upon syngeneic islet transplantation. Islet graft survival was significantly prolonged in mice treated with 2.5HIP NPs, but not NPs containing the insulin B chain peptide 9-23. Protection in 2.5HIP NP-treated mice was attributed both to the simultaneous induction of anergy in 2.5HIP-specific effector T cells and to the expansion of Foxp3+ regulatory T cells specific for the same antigen. Notably, our results indicate that effector function of graft-infiltrating CD4<sup>+</sup> and CD8<sup>+</sup> T cells specific for other β-cell epitopes was significantly impaired, suggesting a novel mechanism of therapeutically induced linked suppression. This work establishes that tolerance induction with a hybrid insulin peptide can delay recurrent autoimmunity in NOD mice, which could inform the development of an Ag-specific therapy for T1D.


2022 ◽  
Author(s):  
Braxton L. Jamison ◽  
James E. DiLisio ◽  
K. Scott Beard ◽  
Tobias Neef ◽  
Brenda Bradley ◽  
...  

The induction of antigen (Ag)-specific tolerance and replacement of islet β-cells are major ongoing goals for the treatment of Type 1 Diabetes (T1D). Our group previously showed that a hybrid insulin peptide (2.5HIP) is a critical autoantigen for diabetogenic CD4<sup>+</sup> T cells in the non-obese diabetic (NOD) mouse model. In this study, we investigated whether induction of Ag-specific tolerance using 2.5HIP-coupled tolerogenic nanoparticles (NPs) could protect diabetic NOD mice from disease recurrence upon syngeneic islet transplantation. Islet graft survival was significantly prolonged in mice treated with 2.5HIP NPs, but not NPs containing the insulin B chain peptide 9-23. Protection in 2.5HIP NP-treated mice was attributed both to the simultaneous induction of anergy in 2.5HIP-specific effector T cells and to the expansion of Foxp3+ regulatory T cells specific for the same antigen. Notably, our results indicate that effector function of graft-infiltrating CD4<sup>+</sup> and CD8<sup>+</sup> T cells specific for other β-cell epitopes was significantly impaired, suggesting a novel mechanism of therapeutically induced linked suppression. This work establishes that tolerance induction with a hybrid insulin peptide can delay recurrent autoimmunity in NOD mice, which could inform the development of an Ag-specific therapy for T1D.


Diabetes ◽  
2022 ◽  
Author(s):  
Braxton L. Jamison ◽  
James E. DiLisio ◽  
K. Scott Beard ◽  
Tobias Neef ◽  
Brenda Bradley ◽  
...  

The induction of antigen (Ag)-specific tolerance and replacement of islet β-cells are major ongoing goals for the treatment of Type 1 Diabetes (T1D). Our group previously showed that a hybrid insulin peptide (2.5HIP) is a critical autoantigen for diabetogenic CD4+ T cells in the non-obese diabetic (NOD) mouse model. In this study, we investigated whether induction of Ag-specific tolerance using 2.5HIP-coupled tolerogenic nanoparticles (NPs) could protect diabetic NOD mice from disease recurrence upon syngeneic islet transplantation. Islet graft survival was significantly prolonged in mice treated with 2.5HIP NPs, but not NPs containing the insulin B chain peptide 9-23. Protection in 2.5HIP NP-treated mice was attributed both to the simultaneous induction of anergy in 2.5HIP-specific effector T cells and to the expansion of Foxp3+ regulatory T cells specific for the same antigen. Notably, our results indicate that effector function of graft-infiltrating CD4+ and CD8+ T cells specific for other β-cell epitopes was significantly impaired, suggesting a novel mechanism of therapeutically induced linked suppression. This work establishes that tolerance induction with a hybrid insulin peptide can delay recurrent autoimmunity in NOD mice, which could inform the development of an Ag-specific therapy for T1D.


Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1439
Author(s):  
Kevin M. Dennehy ◽  
Eva Löll ◽  
Christine Dhillon ◽  
Johanna-Maria Classen ◽  
Tobias D. Warm ◽  
...  

Memory T-cell responses following infection with coronaviruses are reportedly long-lived and provide long-term protection against severe disease. Whether vaccination induces similar long-lived responses is not yet clear since, to date, there are limited data comparing memory CD4+ T-cell responses induced after SARS-CoV-2 infection versus following vaccination with BioNTech/Pfizer BNT162b2. We compared T-cell immune responses over time after infection or vaccination using ELISpot, and memory CD4+ T-cell responses three months after infection/vaccination using activation-induced marker flow cytometric assays. Levels of cytokine-producing T-cells were remarkably stable between three and twelve months after infection, and were comparable to IFNγ+ and IFNγ+IL-2+ T-cell responses but lower than IL-2+ T-cell responses at three months after vaccination. Consistent with this finding, vaccination and infection elicited comparable levels of SARS-CoV-2 specific CD4+ T-cells after three months in addition to comparable proportions of specific central memory CD4+ T-cells. By contrast, the proportions of specific effector memory CD4+ T-cells were significantly lower, whereas specific effector CD4+ T-cells were higher after infection than after vaccination. Our results suggest that T-cell responses—as measured by cytokine expression—and the frequencies of SARS-CoV-2-specific central memory CD4+T-cells—indicative of the formation of the long-lived memory T-cell compartment—are comparably induced after infection and vaccination.


Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1273
Author(s):  
Kirill Vasilyev ◽  
Anna-Polina Shurygina ◽  
Natalia Zabolotnykh ◽  
Mariia Sergeeva ◽  
Ekaterina Romanovskaya-Romanko ◽  
...  

BCG is the only licensed vaccine against Mycobacterium tuberculosis (M.tb) infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which are indispensable for antituberculosis protection. Recently we described the protective efficacy of new mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing TB10.4 and HspX proteins of M.tb within an NS1 influenza protein open reading frame. In the present work, the innate and adaptive immune response to immunization with the Flu/THSP and the immunological properties of vaccine candidate in the BCG-prime → Flu/THSP vector boost vaccination scheme are studied in mice. It was shown that the mucosal administration of Flu/THSP induces the incoming of interstitial macrophages in the lung tissue and stimulates the expression of co-stimulatory CD86 and CD83 molecules on antigen-presenting cells. The T-cellular immune response to Flu/THSP vector was mediated predominantly by the IFNγ-producing CD8+ lymphocytes. BCG-prime → Flu/THSP vector boost immunization scheme was shown to protect mice from severe lung injury caused by M.tb infection due to the enhanced T-cellular immune response, mediated by antigen-specific effector and central memory CD4+ and CD8+ T-lymphocytes.


Author(s):  
Thaís Regina Boufleur ◽  
Nelson Sidnei Massola Júnior ◽  
Ísis Tikami ◽  
Serenella Ana Sukno ◽  
Michael Ronald Thon ◽  
...  

Colletotrichum is one of the most important plant pathogenic genera of fungi due to its scientific and economic impact. Colletotrichum spp. can infect a wide range of hosts, causing losses in crops of major importance worldwide, such as soybean. In the past, soybean anthracnose was mainly caused by C. truncatum, but during the last decade, other species have been identified at an increasing rate, becoming one of the most important limiting factors to soybean production in several regions. To gain a better understanding of the evolutionary origin of soybean anthracnose, we compared the repertoire of effector candidates of four Colletotrichum species pathogenic to soybean and eight pathogens of other hosts. Our results show that the four species infecting soybean belong to two lineages and do not share any of the lineage specific effector candidates identified. These results strongly suggest that two Colletotrichum lineages have acquired the capability to infect soybean independently. This study also provides, for each lineage, a set of candidate effectors encoding genes that may have important roles in pathogenicity towards soybean offering a new resource useful for further research on soybean anthracnose management.


Author(s):  
Diaa Albitar ◽  
R. Jailani ◽  
Megat Syahirul Amin Megat Ali ◽  
Anwar P. P. Abdul Majeed

<p>Robotic prosthetics is increasingly adopted as an enabling technology for amputees. These are vital not only for activities of daily living but to display expression and affection. A vital element to this system is an intelligent model that can identify signatures from the remaining limb that can be mapped to specific effector movements. Therefore, the study proposes the use of forearm electromyogram to classify between different types of hand gestures; fingers spread, wave out, wave in, fist, double tap, and relaxed state. Data are acquired from 32 subjects using Myo armband. Initially, a total of 248 time-and frequency-domain features are extracted from the eightchannel device. Neighborhood component analysis has reduced them to a total of fourteen features. A hand gesture classification model based on electromyogram signal has been successfully developed using support vector machine with overall accuracy of 97.4% for training, and 88.0% for testing.</p>


2021 ◽  
Author(s):  
Michael Müller ◽  
Johann Volzke ◽  
Behnam Subin ◽  
Silke Müller ◽  
Martina Sombetzki ◽  
...  

AbstractWhile vaccination programs against SARS-CoV-2 are globally ongoing, disparate strategies for the deployment of spike antigen show varying effectiveness. In order to explore this phenomenon, we sought to compare the early immune responses against AZD1222 and BNT162b2. SARS-CoV-2 seronegative participants received a single dose of either vaccine and were analyzed for immune cell, effector T cell and antibody dynamics. AZD1222 induced transient leukopenia and major changes among innate and adaptive subpopulations. Both vaccines induced spike protein specific effector T cells which were dominated by Th1 responses following AZD1222 vaccination. A significant reduction of anti-inflammatory T cells upon re-stimulation was also restricted to AZD1222 vaccinees. While IgM and IgG were the dominant isotypes elicited by AZD1222, BNT162b2 led to a significant production of IgG and IgA. Our results suggest that the strategy for spike antigen delivery impacts on how and to what extent immune priming against the main SARS-CoV-2 antigen proceeds.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Geraldine Nouailles ◽  
Emanuel Wyler ◽  
Peter Pennitz ◽  
Dylan Postmus ◽  
Daria Vladimirova ◽  
...  

AbstractIn COVID-19, immune responses are key in determining disease severity. However, cellular mechanisms at the onset of inflammatory lung injury in SARS-CoV-2 infection, particularly involving endothelial cells, remain ill-defined. Using Syrian hamsters as a model for moderate COVID-19, we conduct a detailed longitudinal analysis of systemic and pulmonary cellular responses, and corroborate it with datasets from COVID-19 patients. Monocyte-derived macrophages in lungs exert the earliest and strongest transcriptional response to infection, including induction of pro-inflammatory genes, while epithelial cells show weak alterations. Without evidence for productive infection, endothelial cells react, depending on cell subtypes, by strong and early expression of anti-viral, pro-inflammatory, and T cell recruiting genes. Recruitment of cytotoxic T cells as well as emergence of IgM antibodies precede viral clearance at day 5 post infection. Investigating SARS-CoV-2 infected Syrian hamsters thus identifies cell type-specific effector functions, providing detailed insights into pathomechanisms of COVID-19 and informing therapeutic strategies.


2021 ◽  
Author(s):  
Jennifer Uhrlaub ◽  
Mladen Jergović ◽  
Christine M. Bradshaw ◽  
Sandip Sonar ◽  
Christoper P. Coplen ◽  
...  

Many older humans and animals exhibit reduced immune responses to infection and vaccination, and this often directly correlates to the numbers and frequency of naive T (Tn) cells. We found such a correlation between reduced numbers of blood CD8+ Tn cells and severe clinical outcomes of WNV in both humans naturally exposed to, and mice experimentally infected with, West Nile virus (WNV). To examine possible causality, we sought to increase the number of CD8 Tn cells by treating C57BL/6 mice with IL-7 complexes (IL-7C, anti-IL-7 mAb bound to IL-7), shown previously to efficiently increase peripheral T cell numbers by homeostatic proliferation. T cells underwent robust expansion following IL-7C administration to old mice increasing the number of total T cells (>four-fold) and NS4b:H-2Db-restricted antigen-specific CD8 T cells (two-fold). This improved the numbers of NS4b-specific CD8 T cells detected at the peak of the response against WNV, but not survival in the face of WNV challenge. IL-7C treated old animals also showed no improvement in WNV-specific effector immunity (neutralizing antibody and in vivo T cell cytotoxicity). To test quantitative limits to which CD8 Tn cell restoration could improve protective immunity, we transferred graded doses of Ag-specific precursors into old mice, and showed that injection of 5,400 (but not of 1,800 or 600) adult naive WNV-specific CD8 T cells significantly increased survival after WNV. These results set quantitative limits to the level of Tn reconstitution necessary to improve immune defense in older organisms, and are discussed in light of targets of immune reconstitution.


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