scholarly journals Peripheral and lung resident T cell responses against SARS-CoV-2

2021 ◽  
Author(s):  
Judith Grau-Expósito ◽  
Nerea Sánchez-Gaona ◽  
Núria Massana ◽  
Marina Suppi ◽  
Antonio Astorga-Gamaza ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
T Cell Responses ◽  
Lung Parenchyma ◽  
Viral Proteins ◽  
Viral Spread ◽  
Cell Responses ◽  
Circulating Lymphocytes ◽  
Resident Memory T Cells

Abstract Considering that SARS-CoV-2 interacts with the host at the respiratory tract mucosal interface, T cells strategically placed within these surfaces, namely resident memory T cells, will be essential to limit viral spread and disease. Importantly, these cells are mostly non-recirculating, which reduces the window of opportunity to examine circulating lymphocytes in blood as they home to the lung parenchyma. Here, we demonstrate that viral specific T cells can migrate and establish in the lung as resident memory T cells remaining detectable up to 10 months after initial infection. Moreover, focusing on the acute phase of the infection, we identified virus-specific T cell responses in blood with functional, migratory and apoptotic patterns modulated by viral proteins and associated with clinical outcome. Our study highlights IL-10 secretion by virus-specific T cells associated to a better outcome and the persistence of resident memory T cells as key players for future protection against SARS-CoV-2 infection.

scholarly journals Peripheral and lung resident T cell responses against SARS-CoV-2

2020 ◽  
Author(s):  
Judith Grau-Expósito ◽  
Nerea Sánchez-Gaona ◽  
Núria Massana ◽  
Marina Suppi ◽  
Antonio Astorga-Gamaza ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
T Cell Responses ◽  
Lung Parenchyma ◽  
Viral Proteins ◽  
Viral Spread ◽  
Cell Responses ◽  
Circulating Lymphocytes ◽  
Resident Memory T Cells

SUMMARYConsidering that SARS-CoV-2 interacts with the host at the respiratory tract mucosal interface, T cells strategically placed within these surfaces, namely resident memory T cells, will be essential to limit viral spread and disease. Importantly, these cells are mostly non-recirculating, which reduces the window of opportunity to examine circulating lymphocytes in blood as they home to the lung parenchyma. Here, we demonstrate that viral specific T cells can migrate and establish in the lung as resident memory T cells, being detectable beyond 7 months in convalescent COVID-19 patients. Moreover, focusing on the acute phase of the infection, we identified virus-specific T cell responses in blood with functional, migratory and apoptotic patterns modulated by viral proteins and associated with clinical outcome. Our study highlights IL-10 secretion by virus-specific T cells associated to a better outcome and the persistence of resident memory T cells as key players for future protection against SARS-CoV-2 infection.

scholarly journals Peripheral and lung resident memory T cell responses against SARS-CoV-2

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Judith Grau-Expósito ◽  
Nerea Sánchez-Gaona ◽  
Núria Massana ◽  
Marina Suppi ◽  
Antonio Astorga-Gamaza ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Acute Infection ◽  
T Cell Responses ◽  
Lung Parenchyma ◽  
Viral Proteins ◽  
Memory T Cell ◽  
Cell Responses ◽  
Resident Memory T Cells

AbstractResident memory T cells (TRM) positioned within the respiratory tract are probably required to limit SARS-CoV-2 spread and COVID-19. Importantly, TRM are mostly non-recirculating, which reduces the window of opportunity to examine these cells in the blood as they move to the lung parenchyma. Here, we identify circulating virus-specific T cell responses during acute infection with functional, migratory and apoptotic patterns modulated by viral proteins and associated with clinical outcome. Disease severity is associated predominantly with IFNγ and IL-4 responses, increased responses against S peptides and apoptosis, whereas non-hospitalized patients have increased IL-12p70 levels, degranulation in response to N peptides and SARS-CoV-2-specific CCR7+ T cells secreting IL-10. In convalescent patients, lung-TRM are frequently detected even 10 months after initial infection, in which contemporaneous blood does not reflect tissue-resident profiles. Our study highlights a balanced anti-inflammatory antiviral response associated with a better outcome and persisting TRM cells as important for future protection against SARS-CoV-2 infection.

scholarly journals Detection of IFNγ-Secreting CD4+ and CD8+ Memory T Cells in COVID-19 Convalescents after Stimulation of Peripheral Blood Mononuclear Cells with Live SARS-CoV-2

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1490
Author(s):  
Victoria Matyushenko ◽  
Irina Isakova-Sivak ◽  
Igor Kudryavtsev ◽  
Arina Goshina ◽  
Anna Chistyakova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Natural Infection ◽  
Intracellular Cytokine Staining ◽  
T Cell Responses ◽  
Effector Memory ◽  
Memory T Cell ◽  
Cell Responses ◽  
Stimulation Of

Background: New coronavirus SARS-CoV-2, a causative agent of the COVID-19 pandemic, has been circulating among humans since November 2019. Multiple studies have assessed the qualitative and quantitative characteristics of virus-specific immunity in COVID-19 convalescents, however, some aspects of the development of memory T-cell responses after natural SARS-CoV-2 infection remain uncovered. Methods: In most of published studies T-cell immunity to the new coronavirus is assessed using peptides corresponding to SARS-CoV-1 or SARS-CoV-2 T-cell epitopes, or with peptide pools covering various parts of the viral proteins. Here, we determined the level of CD4+ and CD8+ memory T-cell responses in COVID-19 convalescents by stimulating PBMCs collected 1 to 6 months after recovery with sucrose gradient-purified live SARS-CoV-2. IFNγ production by the central and effector memory helper and cytotoxic T cells was assessed by intracellular cytokine staining assay and flow cytometry. Results: Stimulation of PBMCs with live SARS-CoV-2 revealed IFNγ-producing T-helper effector memory cells with CD4+CD45RA−CCR7− phenotype, which persisted in circulation for up to 6 month after COVID-19. In contrast, SARS-CoV-2-specific IFNγ-secreting cytotoxic effector memory T cells were found at significant levels only shortly after the disease, but rapidly decreased over time. Conclusion: The stimulation of immune cells with live SARS-CoV-2 revealed a rapid decline in the pool of effector memory CD8+, but not CD4+, T cells after recovery from COVID-19. These data provide additional information on the development and persistence of cellular immune responses after natural infection, and can inform further development of T cell-based SARS-CoV-2 vaccines.

scholarly journals Baseline Levels of Influenza-Specific CD4 Memory T-Cells Affect T-Cell Responses to Influenza Vaccines

PLoS ONE ◽  
2008 ◽  
Vol 3 (7) ◽  
pp. e2574 ◽  
Author(s):  
Xiao-Song He ◽  
Tyson H. Holmes ◽  
Sanae Sasaki ◽  
Maria C. Jaimes ◽  
George W. Kemble ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
T Cell Responses ◽  
Influenza Vaccines ◽  
Cell Responses ◽  
Baseline Levels

scholarly journals Alternative Serotype Adenovirus Vaccine Vectors Elicit Memory T Cells with Enhanced Anamnestic Capacity Compared to Ad5 Vectors

2012 ◽  
Vol 87 (3) ◽  
pp. 1373-1384 ◽  
Author(s):  
Pablo Penaloza-MacMaster ◽  
Nicholas M. Provine ◽  
Joshua Ra ◽  
Erica N. Borducchi ◽  
Anna McNally ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Lymphocytic Choriomeningitis ◽  
Phenotypic Differences ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Serotype 5

ABSTRACTThe failure of the adenovirus serotype 5 (Ad5) vector-based human immunodeficiency virus type 1 (HIV-1) vaccine in the STEP study has led to the development of adenovirus vectors derived from alternative serotypes, such as Ad26, Ad35, and Ad48. We have recently demonstrated that vaccines using alternative-serotype Ad vectors confer partial protection against stringent simian immunodeficiency virus (SIV) challenges in rhesus monkeys. However, phenotypic differences between the T cell responses elicited by Ad5 and those of alternative-serotype Ad vectors remain unexplored. Here, we report the magnitude, phenotype, functionality, and recall capacity of memory T cell responses elicited in mice by Ad5, Ad26, Ad35, and Ad48 vectors expressing lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP). Our data demonstrate that memory T cells elicited by Ad5 vectors were high in magnitude but exhibited functional exhaustion and decreased anamnestic potential following secondary antigen challenge compared to Ad26, Ad35, and Ad48 vectors. These data suggest that vaccination with alternative-serotype Ad vectors offers substantial immunological advantages over Ad5 vectors, in addition to circumventing high baseline Ad5-specific neutralizing antibody titers.

scholarly journals Impaired Lymphoid Chemokine-Mediated Migration due to a Block on the Chemokine Receptor Switch in Human Cytomegalovirus-Infected Dendritic Cells

2004 ◽  
Vol 78 (6) ◽  
pp. 3046-3054 ◽  
Author(s):  
Magdalena Moutaftsi ◽  
Paul Brennan ◽  
Stephen A. Spector ◽  
Zsuzsanna Tabi
Keyword(s):  
T Cells ◽  
T Cell ◽  
Human Cytomegalovirus ◽  
T Cell Activation ◽  
Chemokine Receptor ◽  
Cell Activation ◽  
T Cell Responses ◽  
Viral Interference ◽  
Viral Spread ◽  
Cell Responses

ABSTRACT Dendritic cell (DC) migration from the site of infection to the site of T-cell priming is a crucial event in the generation of antiviral T-cell responses. Here we present to our knowledge the first functional evidence that human cytomegalovirus (HCMV) blocks the migration of infected monocyte-derived DCs toward lymphoid chemokines CCL19 and CCL21. DC migration is blocked by viral impairment of the chemokine receptor switch at the level of the expression of CCR7 molecules. The inhibition occurs with immediate-early-early kinetics, and viral interference with NF-κB signaling is likely to be at least partially responsible for the lack of CCR7 expression. DCs which migrate from the infected cultures are HCMV antigen negative, and consequently they do not stimulate HCMV-specific CD8+ T cells, while CD4+-T-cell activation is not impaired. Although CD8+ T cells can also be activated by alternative antigen presentation mechanisms, the spatial segregation of naive T cells and infected DCs seems a potent mechanism of delaying the generation of primary CD8+-T-cell responses and aiding early viral spread.

scholarly journals Chlamydia pneumoniae-Induced Memory CD4+ T-Cell Activation in Human Peripheral Blood Correlates with Distinct Antibody Response Patterns

2010 ◽  
Vol 17 (5) ◽  
pp. 705-712 ◽  
Author(s):  
Sebastian Bunk ◽  
Hanne Schaffert ◽  
Bianca Schmid ◽  
Christoph Goletz ◽  
Sabine Zeller ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Chlamydia Pneumoniae ◽  
Memory T Cells ◽  
T Cell Responses ◽  
Cell Responses ◽  
Ifn Γ

ABSTRACT Chlamydia pneumoniae is a frequent pathogen of the respiratory tract, and persistent infections with this obligate intracellular bacterium have been associated with different severe sequelae. Although T-cell activation during acute C. pneumoniae infections has been described, little is known about the frequency or the role of the C. pneumoniae-specific memory T cells that reside in the human body after the resolution of the infection. In the present study, the C. pneumoniae-induced T-cell responses in peripheral blood mononuclear cells of 56 healthy volunteers were analyzed and compared to the donor's serum antibody reactivity toward whole C. pneumoniae as well as recombinant C. pneumoniae antigens. Following short-term stimulation with C. pneumoniae, both gamma interferon (IFN-γ)- and interleukin-2 (IL-2)-producing CD4+ T-cell responses could be detected in 16 of 56 healthy individuals. C. pneumoniae-activated CD4+ T cells expressed CD154, a marker for T-cell receptor-dependent activation, and displayed a phenotype of central memory T cells showing dominant IL-2 production but also IFN-γ production. Interestingly, individuals with both IFN-γ- and IL-2-producing responses showed significantly decreased immunoglobulin G reactivity toward C. pneumoniae RpoA and DnaK, antigens known to be strongly upregulated during chlamydial persistence, compared to IgG reactivity of seropositive individuals with no T-cell response or CD4+ T-cell responses involving the production of a single cytokine (IFN-γ or IL-2). Our results demonstrate that memory CD4+ T cells responding to C. pneumoniae stimulation can be detected in the circulation of healthy donors. Furthermore, among seropositive individuals, the presence or the absence of dual IFN-γ- and IL-2-producing T-cell responses was associated with distinct patterns of antibody responses toward persistence-associated C. pneumoniae antigens.

scholarly journals SARS-CoV-2-specific T Cell Memory is Sustained in COVID-19 Convalescents for 8 Months with Successful Development of Stem Cell-like Memory T Cells

2021 ◽  
Author(s):  
Jae Hyung Jung ◽  
Min-Seok Rha ◽  
Moa Sa ◽  
Hee Kyoung Choi ◽  
Ji Hoon Jeon ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Memory T Cells ◽  
Ex Vivo ◽  
T Cell Responses ◽  
Mhc I ◽  
Cell Responses ◽  
Proliferation Capacity ◽  
Specific Memory

AbstractMemory T cells contribute to rapid viral clearance during re-infection, but the longevity and differentiation of SARS-CoV-2-specific memory T cells remain unclear. We conducted direct ex vivo assays to evaluate SARS-CoV-2-specific CD4+ and CD8+ T cell responses in COVID-19 convalescents up to 254 days post-symptom onset (DPSO). Here, we report that memory T cell responses were maintained during the study period. In particular, we observed sustained polyfunctionality and proliferation capacity of SARS-CoV-2-specific T cells. Among SARS-CoV-2-specific CD4+ and CD8+ T cells detected by activation-induced markers, the proportion of stem cell-like memory T (TSCM) cells increased, peaking at approximately 120 DPSO. Development of TSCM cells was confirmed by SARS-CoV-2-specific MHC-I multimer staining. Considering the self-renewal capacity and multipotency of TSCM cells, our data suggest that SARS-CoV-2-specific T cells are long-lasting after recovery from COVID-19. The current study provides insight for establishing an effective vaccination program and epidemiological measurement.

scholarly journals Solid Tumor Microenvironment Can Harbor and Support Functional Properties of Memory T Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Peter M. Sullivan ◽  
Steven James Reed ◽  
Vandana Kalia ◽  
Surojit Sarkar
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Cd8 T Cells ◽  
Solid Tumor ◽  
Memory T Cells ◽  
T Cell Responses ◽  
Antigenic Stimulation ◽  
Cell Responses

Robust T cell responses are crucial for effective anti-tumor responses and often dictate patient survival. However, in the context of solid tumors, both endogenous T cell responses and current adoptive T cell therapies are impeded by the immunosuppressive tumor microenvironment (TME). A multitude of inhibitory signals, suppressive immune cells, metabolites, hypoxic conditions and limiting nutrients are believed to render the TME non-conducive to sustaining productive T cell responses. In this study we conducted an in-depth phenotypic and functional comparison of tumor-specific T cells and tumor-nonspecific bystander memory T cells within the same TME. Using two distinct TCR transgenic and solid-tumor models, our data demonstrate that despite exposure to the same cell-extrinsic factors of the TME, the tumor-nonspecific bystander CD8 T cells retain the complete panoply of memory markers, and do not share the same exhaustive phenotype as tumor-reactive T cells. Compared to tumor-specific T cells, bystander memory CD8 T cells in the TME also retain functional effector cytokine production capabilities in response to ex vivo cognate antigenic stimulation. Consistent with these results, bystander memory T cells isolated from tumors showed enhanced recall responses to secondary bacterial challenge in a T cell transplant model. Importantly, the tumor-resident bystander memory cells could also efficiently utilize the available resources within the TME to elaborate in situ recall effector functions following intra-tumoral peptide antigen injection. Additionally, CRISPR-Cas9 gene deletion studies showed that CXCR3 was critical for the trafficking of both tumor antigen-specific and bystander memory T cells to solid tumors. Collectively, these findings that T cells can persist and retain their functionality in distinct solid tumor environments in the absence of cognate antigenic stimulation, support the notion that persistent antigenic signaling is the central driver of T cell exhaustion within the TME. These studies bear implications for programming more efficacious TCR- and CAR-T cells with augmented therapeutic efficacy and longevity through regulation of antigen and chemokine receptors.

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