scholarly journals Impact of pre-existing T cell immunity to SARS-CoV-2 in uninfected individuals with COVID-19 mortality in different countries

2020 ◽  
Author(s):  
Gennadi V. Glinsky
Keyword(s):  
T Cells ◽  
T Cell ◽  
Herd Immunity ◽  
Inverse Correlation ◽  
Mortality Rates ◽  
Virus Spread ◽  
Cell Reactivity ◽  
Cell Immunity ◽  
Potential Impact ◽  
T Cell Reactivity

AbstractSeveral recent studies identified SARS-CoV-2 reactive T cells in people without exposure to the virus. However, pathophysiological implications of these findings remain unknown. Here, the potential impact of pre-existing T cell reactivity against SARS-CoV-2 in uninfected individuals on markedly different COVID-19 mortality levels in different countries has been investigated. The inverse correlation is documented between the prevalence of pre-existing SARS-CoV-2 reactive T cells in people without exposure to the virus and COVID-19 mortality rates in different countries. In countries with similar levels of pre-existing SARS-CoV-2 cross-reactive T cells in uninfected individuals, differences in COVID-19 mortality appear linked with the extend and consistency of implementations of social measures designed to limit the transmission of SARS-CoV-2 (lockdown; physical distancing; mask wearing). Collectively, these observations support the model that the level of pre-existing SARS-CoV-2 reactive T cells is one of the important determinants of the innate herd immunity against COVID-19. Together with the consistent social measures directed to limit the virus spread, high levels of pre-existing SARS-CoV-2 reactive T cells appear significant determinants diminishing the COVID-19 mortality. Observations reported in this contribution should have significant impact on definitions of the herd immunity threshold required to effectively stop the pandemic in different countries across the globe.

scholarly journals Cytomegalovirus-specific T-cell reactivity in biliary atresia at the time of diagnosis is associated with deficits in regulatory T cells

Hepatology ◽  
2012 ◽  
Vol 55 (4) ◽  
pp. 1130-1138 ◽  
Author(s):  
Stephen M. Brindley ◽  
Allison M. Lanham ◽  
Frederick M. Karrer ◽  
Rebecca M. Tucker ◽  
Andrew P. Fontenot ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Biliary Atresia ◽  
Cell Reactivity ◽  
T Cell Reactivity

scholarly journals Evaluation of T Cell Immunity against Human Cytomegalovirus: Impact on Patient Management and Risk Assessment of Vertical Transmission

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Giulia Freer ◽  
Paola Quaranta ◽  
Mauro Pistello
Keyword(s):  
T Cell ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Infectious Agents ◽  
Cmv Infection ◽  
Active Infection ◽  
Cell Reactivity ◽  
Cell Immunity ◽  
Pros And Cons ◽  
T Cell Reactivity

Cytomegalovirus (CMV) is one of the most common infectious agents, infecting the general population at an early age without causing morbidity most of the time. However, on particular occasions, it may represent a serious risk, as active infection is associated with rejection and disease after solid organ transplantation or fetal transmission during pregnancy. Several methods for CMV diagnosis are available on the market, but because infection is so common, careful selection is needed to discriminate primary infection from reactivation. This review focuses on methods based on CMV-specific T cell reactivity to help monitor the consequences of CMV infection/reactivation in specific categories of patients. This review makes an attempt at discussing the pros and cons of the methods available.

scholarly journals HCoV- and SARS-CoV-2 Cross-Reactive T Cells in CVID Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Sophie Steiner ◽  
Franziska Sotzny ◽  
Sandra Bauer ◽  
Il-Kang Na ◽  
Michael Schmueck-Henneresse ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Cell Responses ◽  
Cross Reactivity ◽  
T Cell Immunity ◽  
Cell Reactivity ◽  
Cd8 Cells ◽  
Cell Responses ◽  
Cell Immunity

The inability of patients with CVID to mount specific antibody responses to pathogens has raised concerns on the risk and severity of SARS-CoV-2 infection, but there might be a role for protective T cells in these patients. SARS-CoV-2 reactive T cells have been reported for SARS-CoV-2 unexposed healthy individuals. Until now, there is no data on T cell immunity to SARS-CoV-2 infection in CVID. This study aimed to evaluate reactive T cells to human endemic corona viruses (HCoV) and to study pre-existing SARS-CoV-2 reactive T cells in unexposed CVID patients. We evaluated SARS-CoV-2- and HCoV-229E and –OC43 reactive T cells in response to seven peptide pools, including spike and nucleocapsid (NCAP) proteins, in 11 unexposed CVID, 12 unexposed and 11 post COVID-19 healthy controls (HC). We further characterized reactive T cells by IFNγ, TNFα and IL-2 profiles. SARS-CoV-2 spike-reactive CD4+ T cells were detected in 7 of 11 unexposed CVID patients, albeit with fewer multifunctional (IFNγ/TNFα/IL-2) cells than unexposed HC. CVID patients had no SARS-CoV-2 NCAP reactive CD4+ T cells and less reactive CD8+ cells compared to unexposed HC. We observed a correlation between T cell reactivity against spike of SARS-CoV-2 and HCoVs in unexposed, but not post COVID-19 HC, suggesting cross-reactivity. T cell responses in post COVID-19 HC could be distinguished from unexposed HC by higher frequencies of triple-positive NCAP reactive CD4+ T cells. Taken together, SARS-CoV-2 reactive T cells are detectable in unexposed CVID patients albeit with lower recognition frequencies and polyfunctional potential. Frequencies of triple-functional reactive CD4+ cells might provide a marker to distinguish HCoV cross-reactive from SARS-CoV-2 specific T cell responses. Our data provides evidence, that anti-viral T cell immunity is not relevantly impaired in most CVID patients.

scholarly journals The RIG-I Agonist 3pRNA Synergizes with Checkpoint Blockade in Cancer Immunotherapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3436-3436 ◽  
Author(s):  
Simon Heidegger ◽  
Diana Kreppel ◽  
Michael Bscheider ◽  
Alexander Wintges ◽  
Sarah Bek ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Immunity ◽  
Conflicts Of Interest ◽  
Cytotoxic T Cells ◽  
Type I ◽  
Therapeutic Success ◽  
Cell Reactivity ◽  
T Cell Reactivity ◽  
Systemic Antibiotics

Abstract Antibody-mediated targeting of regulatory T cell receptors such as CTLA-4 has been shown to enhance anti-tumor immune responses against several cancer entities including malignant melanoma. Yet, therapeutic success in patients remains variable underscoring the need for novel combinatorial approaches. Here we established a vaccination protocol that combines selective engagement of the nucleic acid-sensing pattern recognition receptor RIG-I, antigen and CTLA-4-blockade. We found that vaccination together with RIG-I ligation strongly synergized with CTLA-4 blockade to induce expansion and activation of antigen-specific CD8+ T cells and potent anti-tumor immunity. Cross-priming of cytotoxic T cells as well as anti-tumor immunity required the adapter protein MAVS and type I interferon (IFN) signaling and were mediated by dendritic cells. In addition, the benefit of the combined immunization with anti-CTLA-4 was reduced by systemic antibiotics pointing to the requisite of an intact commensal microbiota in this context. Together, our findings describe a novel combinatorial strategy that may form the basis for the design of new type I IFN-based regimens that enhance antigen-specific T cell reactivity against cancer. Disclosures No relevant conflicts of interest to declare.

scholarly journals Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells

2005 ◽  
Vol 202 (7) ◽  
pp. 907-912 ◽  
Author(s):  
Luca Gattinoni ◽  
Steven E. Finkelstein ◽  
Christopher A. Klebanoff ◽  
Paul A. Antony ◽  
Douglas C. Palmer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Adoptive Cell Transfer ◽  
Peripheral Tolerance ◽  
Antitumor Efficacy ◽  
Cell Reactivity ◽  
T Cell Reactivity ◽  
Homeostatic Cytokines ◽  
Cell Functionality

Depletion of immune elements before adoptive cell transfer (ACT) can dramatically improve the antitumor efficacy of transferred CD8+ T cells, but the specific mechanisms that contribute to this enhanced immunity remain poorly defined. Elimination of CD4+CD25+ regulatory T (T reg) cells has been proposed as a key mechanism by which lymphodepletion augments ACT-based immunotherapy. We found that even in the genetic absence of T reg cells, a nonmyeloablative regimen substantially augmented CD8+ T cell reactivity to self-tissue and tumor. Surprisingly, enhanced antitumor efficacy and autoimmunity was caused by increased function rather than increased numbers of tumor-reactive T cells, as would be expected by homeostatic mechanisms. The γC cytokines IL-7 and IL-15 were required for augmenting T cell functionality and antitumor activity. Removal of γC cytokine–responsive endogenous cells using antibody or genetic means resulted in the enhanced antitumor responses similar to those seen after nonmyeloablative conditioning. These data indicate that lymphodepletion removes endogenous cellular elements that act as sinks for cytokines that are capable of augmenting the activity of self/tumor-reactive CD8+ T cells. Thus, the restricted availability of homeostatic cytokines can be a contributing factor to peripheral tolerance, as well as a limiting resource for the effectiveness of tumor-specific T cells.

scholarly journals Regulatory T cells suppress antigen-driven CD4 T cell reactivity following injury

2010 ◽  
Vol 89 (1) ◽  
pp. 137-147 ◽  
Author(s):  
Malcolm P. MacConmara ◽  
Goro Tajima ◽  
Fionnuala OˈLeary ◽  
Adam J. Delisle ◽  
Ann M. McKenna ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cd4 T Cell ◽  
Cell Reactivity ◽  
T Cell Reactivity

scholarly journals T-Cell Reactivity against Streptococcal Antigens in the Periphery Mirrors Reactivity of Heart-Infiltrating T Lymphocytes in Rheumatic Heart Disease Patients

2001 ◽  
Vol 69 (9) ◽  
pp. 5345-5351 ◽  
Author(s):  
Luiza Guilherme ◽  
Sandra E. Oshiro ◽  
Kellen C. Faé ◽  
Edécio Cunha-Neto ◽  
Guilherme Renesto ◽  
...  
Keyword(s):  
T Cells ◽  
Heart Disease ◽  
T Cell ◽  
Rheumatic Heart Disease ◽  
Peripheral Blood ◽  
Cell Reactivity ◽  
T Cell Clones ◽  
Cell Clones ◽  
T Cell Reactivity ◽  
Rheumatic Heart

ABSTRACT T-cell molecular mimicry between streptococcal and heart proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic heart disease (RHD). We searched for immunodominant T-cell M5 epitopes among RHD patients with defined clinical outcomes and compared the T-cell reactivities of peripheral blood and intralesional T cells from patients with severe RHD. The role of HLA class II molecules in the presentation of M5 peptides was also evaluated. We studied the T-cell reactivity against M5 peptides and heart proteins on peripheral blood mononuclear cells (PBMC) from 74 RHD patients grouped according to the severity of disease, along with intralesional and peripheral T-cell clones from RHD patients. Peptides encompassing residues 1 to 25, 81 to 103, 125 to 139, and 163 to 177 were more frequently recognized by PBMC from RHD patients than by those from controls. The M5 peptide encompassing residues 81 to 96 [M5(81–96) peptide] was most frequently recognized by PBMC from HLA-DR7+DR53+ patients with severe RHD, and 46.9% (15 of 32) and 43% (3 of 7) of heart-infiltrating and PBMC-derived peptide-reactive T-cell clones, respectively, recognized the M5(81–103) region. Heart proteins were recognized more frequently by PBMC from patients with severe RHD than by those from patients with mild RHD. The similar pattern of T-cell reactivity found with both peripheral blood and heart-infiltrating T cells is consistent with the migration of M-protein-sensitized T cells to the heart tissue. Conversely, the presence of heart-reactive T cells in the PBMC of patients with severe RHD also suggests a spillover of sensitized T cells from the heart lesion.

scholarly journals SAT0361 HEALTHY HUMAN SPINAL PROCESSES PERI-ENTHESEAL T-CELLS EXHIBIT A TR1 RATHER THAN A FOXP3 REGULATORY PHENOTYPE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1127.2-1128
Author(s):  
H. Rowe ◽  
A. Watad ◽  
T. Russell ◽  
K. Sharif ◽  
D. Newton ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Growth Factors ◽  
T Cell ◽  
Research Funding ◽  
Research Support ◽  
Healthy Human ◽  
Cell Reactivity ◽  
Funding Support ◽  
T Cell Reactivity

Background:We have previously reported that the normal spinal enthesis has populations of conventional T-cells including CD4+ & CD8+ T-cells that could be induced to produce IL-17A and TNF following anti-CD3/CD28 stimulation. The biology of such cells in health including their normal function and antigen reactivity is completely unknown. The purpose of this work was to define the phenotype, functionality and TCR reactivity of such T-cells in health.Objectives:To investigate whether the T-cells at the normal enthesis were regulatory in nature and to determine the type of regulatory T-cell as Tr1 or FOXP3 regulatory T-cell and to determine T-cell reactivity.Methods:Healthy interspinous ligament and spinous process with matched peripheral blood were harvested from patients undergoing elective spinal surgery (n=20). Entheseal soft tissue (EST) & peri-entheseal bone (PEB) was enzymatically digested and then sorted. Tr1 and Treg phenotypes were investigated using flow cytometry. Analysis of cytokines, growth factors and chemokines was performed by qRT-PCR, ELISA and flow cytometry. TCR sequencing was performed and a search for putative T-cell reactivity was done using TCR3 database.Results:Pro-inflammatory cytokine transcripts including IL-17A, IL-17F, IL-22, IL-23 (p19) & TNF were very low or undetectable in the Enthesis T-cells (Fig 1). Flow cytometry confirmed entheseal T-cells had a Tr1 phenotype (CD4+ LAG3+ CD49b+). Intracellular flow cytometry showed enthesis T-cells had very low FOXP3 expression, when compared to their blood counterparts. Intracellular flow cytometry and gene expression showed high basal expression of growth factors and regulatory proteins such as IL-10 & TGFβ, when compared to blood T-cells. RNA-Seq data, showed 13 potential TCR clonal sequences the most common of which are predicted to be reactive viral infection was CMV present in 8 sequences and Influenza A virus present in 2 sequences.Conclusion:The healthy human enthesis has regulatory T-cells of a Tr1 phenotype rather than a FOXP3 Treg phenotype. Many clones have antigen specificity indicating reactivity to prior infection. These findings suggest that conventional entheseal T-cells have a role in enthesis immune homeostasis.Disclosure of Interests:Hannah Rowe Grant/research support from: Novartis UK Investigator Initiated non-clinical research funding support, Abdulla Watad: None declared, Tobias Russell Grant/research support from: Novartis UK Investigator Initiated non-clinical research funding support, Kassem Sharif: None declared, Darren Newton: None declared, Miriam Wittmann: None declared, Qiao Zhou Grant/research support from: Funded by the PARTNER fellowship program, Almas Khan: None declared, Peter Loughenbury: None declared, Robert Dunsmuir: None declared, Abhay S Rao: None declared, Peter Millner: None declared, Tony Kenna: None declared, Matthew Brown: None declared, Charlie Bridgewood: None declared, Dennis McGonagle Grant/research support from: Janssen Research & Development, LLC

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