scholarly journals Persistent cellular immunity to SARS-CoV-2 infection

2021 ◽  
Vol 218 (4) ◽  
Author(s):  
Gaëlle Breton ◽  
Pilar Mendoza ◽  
Thomas Hägglöf ◽  
Thiago Y. Oliveira ◽  
Dennis Schaefer-Babajew ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cell Division ◽  
T Cell ◽  
Cellular Immunity ◽  
Memory T Cells ◽  
Cell Responses ◽  
Paired Samples ◽  
Specific Memory ◽  
Cd8 Memory T Cells

SARS-CoV-2 is responsible for an ongoing pandemic that has affected millions of individuals around the globe. To gain further understanding of the immune response in recovered individuals, we measured T cell responses in paired samples obtained an average of 1.3 and 6.1 mo after infection from 41 individuals. The data indicate that recovered individuals show persistent polyfunctional SARS-CoV-2 antigen–specific memory that could contribute to rapid recall responses. Recovered individuals also show enduring alterations in relative overall numbers of CD4+ and CD8+ memory T cells, including expression of activation/exhaustion markers, and cell division.

scholarly journals Persistent Cellular Immunity to SARS-CoV-2 Infection

2020 ◽  
Author(s):  
Gaëlle Breton ◽  
Pilar Mendoza ◽  
Thomas Hagglof ◽  
Thiago Y. Oliveira ◽  
Dennis Schaefer-Babajew ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cell Division ◽  
T Cell ◽  
T Cell Responses ◽  
Memory T Cell ◽  
Cell Responses ◽  
Paired Samples ◽  
Specific Memory ◽  
Immune Alterations

AbstractSARS-CoV-2 is responsible for an ongoing pandemic that affected millions of individuals around the globe. To gain further understanding of the immune response in recovered individuals we measured T cell responses in paired samples obtained an average of 1.3 and 6.1 months after infection from 41 individuals. The data indicate that recovered individuals show persistent polyfunctional SARS-CoV-2 antigen specific memory that could contribute to rapid recall responses. In addition, recovered individuals show enduring immune alterations in relative numbers of CD4+ and CD8+ T cells, expression of activation/exhaustion markers, and cell division.SummaryWe show that SARS-CoV-2 infection elicits broadly reactive and highly functional memory T cell responses that persist 6 months after infection. In addition, recovered individuals show enduring immune alterations in CD4+ and CD8+ T cells compartments.

scholarly journals CD4 memory T cells survive and proliferate but fail to differentiate in the absence of CD40

2006 ◽  
Vol 203 (4) ◽  
pp. 897-906 ◽  
Author(s):  
Megan MacLeod ◽  
Mark J. Kwakkenbos ◽  
Alison Crawford ◽  
Sheila Brown ◽  
Brigitta Stockinger ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Cell Receptor ◽  
Memory Cells ◽  
Cell Stage ◽  
Effector Cells ◽  
Cell Responses ◽  
Histocompatibility Complex ◽  
Specific Memory

Secondary T cell responses are enhanced because of an expansion in numbers of antigen-specific (memory) cells. Using major histocompatibility complex class II tetramers we have tracked peptide-specific endogenous (non–T cell receptor transgenic) CD4 memory T cells in normal and in costimulation-deficient mice. CD4 memory T cells were detectable after immunization for more than 200 days, although decay was apparent. Memory cells generated in CD40 knockout mice by immunization with peptide-pulsed wild-type dendritic cells survived in the absence of CD40 and proliferated when boosted with peptide (plus adjuvant) in a CD40-independent fashion. However, differentiation of the memory cells into cytokine-producing effector cells did not occur in the absence of CD40. The data indicate that memory cells can be generated without passing through the effector cell stage.

scholarly journals The transfer of adaptive immunity to CMV during hematopoietic stem cell transplantation is dependent on the specificity and phenotype of CMV-specific T cells in the donor

Blood ◽  
2009 ◽  
Vol 114 (24) ◽  
pp. 5071-5080 ◽  
Author(s):  
Phillip Scheinberg ◽  
Jan J. Melenhorst ◽  
Jason M. Brenchley ◽  
Brenna J. Hill ◽  
Nancy F. Hensel ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Memory T Cells ◽  
Viral Reactivation ◽  
Hematopoietic Stem ◽  
Cell Responses ◽  
Specific Memory

Abstract The successful reconstitution of adaptive immunity to human cytomegalovirus (CMV) in hematopoietic stem cell transplantation (HSCT) recipients is central to the reduction of viral reactivation-related morbidity and mortality. Here, we characterized the magnitude, specificity, phenotype, function, and clonotypic composition of CMV-specific T-cell responses in 18 donor-recipient pairs both before and after HSCT. The principal findings were: (1) the specificity of CMV-specific T-cell responses in the recipient after HSCT mirrors that in the donor; (2) the maintenance of these targeting patterns reflects the transfer of epitope-specific T-cell clonotypes from donor to recipient; (3) less differentiated CD27+CD57− CMV-specific memory T cells are more likely to persist in the recipient after HSCT compared with more terminally differentiated CD27− CD57+ CMV-specific memory T cells; (4) the presence of greater numbers of less differentiated CD8+ CMV-specific T cells in the donor appears to confer protection against viral reactivation in the recipient after HSCT; and (5) CMV-specific T cells acquire a more differentiated phenotype and a restricted functional profile after HSCT. Overall, these findings define the immunologic factors that influence the successful adoptive transfer of antigen-specific T-cell immunity during HSCT, which enables the identification of recipients at particular risk of CMV reactivation after HSCT.

scholarly journals Role of the cellular immunity in the formation of the immune response in coronavirus infections

2021 ◽  
Vol 23 (6) ◽  
pp. 1229-1238
Author(s):  
I. A. Ivanova ◽  
N. D. Omelchenko ◽  
A. V. Filippenko ◽  
A. A. Trufanova ◽  
A. K. Noskov
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cellular Immunity ◽  
Memory T Cells ◽  
Adaptive Immune Response ◽  
Cell Immune Response ◽  
Adaptive Immune ◽  
Specific Memory ◽  
Causative Agents

The data obtained during previous epidemics caused by coronaviruses, and current pandemic indicate that assessing the role of certain immune interactions between these viruses and the microorganism is the main pre-requisite for development of diagnostic test systems as well as effective medical drugs and preventive measures. The review summarizes the results of studying patho– and immunogenesis of SARSCoV, MERS-CoV, and SARS-CoV-2 infections. These coronaviruses were proven to suppress development of adaptive immune response at the stage of its induction, affecting the number and functional activity of lymphocytes, effectors of cellular immunity, causing impairment of lymphopoiesis, apoptosis and «depletion» of these cells, thus leading to longer duration of the disease and increased viral load. Information about the role of cellular immunity in development of immune response to coronaviruses is presented. It was proven that the causative agents of SARS, MERS and COVID-19 trigger adaptive immune response in the microorganism according to both humoral and cellular types. Moreover, the synthesis of specific immunoglobulins does not yet point to presence of protective immune response. Activation of the cellular link of immunity is also important. A high degree of antigenic epitope homology in SARS-CoV, MERS-CoV and SARS-CoV-2 is described, thus suggesting an opportunity for cross-immunity to coronaviruses. The review addresses issues related to the terms of specific memory immune cells to SARS-CoV, MERS-CoV and SARS-CoV-2, and their role in providing long-term protection against these infections. Given that specific antibodies to SARS and MERS pathogens persisted for a year, were often not detected or briefly registered in patients with mild and asymptomatic infections, we can talk about important role of the cellular immune response in providing immunity to these coronaviruses. It was shown that, in contrast to antibodies, the antigen-specific memory T cells were registered in patients with SARS virus for 4 to 11 years, and Middle East Respiratory Syndrome – up to two years. Further research is needed to determine presence and number of memory T cells in COVID-19. A comparative analysis of data obtained during previous epidemics with respect to formation of adaptive immunity to coronaviruses. Description of proteins and epitopes recognized by human T lymphocytes will be useful in monitoring immune responses in COVID-19 patients, as well as in developing informative tests to study T cell immune response to SARS-CoV-2 and new preventive drugs.

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 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.

443 An immunotherapy trio in advanced HNSCC for coordinated B and T cell antigen response

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A469-A469
Author(s):  
Bernard Fox ◽  
Tarsem Moudgil ◽  
Traci Hilton ◽  
Noriko Iwamoto ◽  
Christopher Paustian ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Data Sets ◽  
Cell Responses ◽  
Anti Cancer ◽  
Bead Arrays ◽  
Hnscc Cell

BackgroundOutcomes for recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) are dismal and responses to anti-PD-1 appear best in tumors with PD-1+ T cells in proximity to PD-L1+ cells, arguing that improved outcome is associated with a pre-existing anti-cancer immune response. Based on this, we hypothesize that vaccines which prime and/or expand T cells to a spectrum of antigens overexpressed by HNSCC combined with T cell agonists, like anti-GITR, that provide costimulatory signals will improve the anti-PD-1 response rates. We have developed a cancer vaccine, DPV-001, that contains more than 300 proteins for genes overexpressed by HNSCC, encapsulated in a CLEC9A-targeted microvesicle and containing TLR/NOD agonists and DAMPs. Recently, we reported that combining anti-GITR + vaccine + anti-PD-1 augmented therapeutic efficacy in a preclinical model and now plan a phase 1b trial of this combination in patients with advanced HNSCC.MethodsSera from patients receiving DPV-001 as adjuvant therapy for definitively treated NSCLC, were analyzed for IgG responses to human proteins by MAP bead arrays and results compared to TCGA gene expression data sets for HNSCC. HNSCC cell lines were evaluated by RNASeq and peptides were eluted from HLA, analyzed by mass spectroscopy and correlated against MAP bead arrays and TCGA data sets. Tumor-reactive T cells from a vaccinated patient were enriched and expanded, and used in cytokine release assay (CRA) against autologous NSCLC and partially HLA matched allogeneic HNSCC cell lines.ResultsPatients receiving DPV-001 (N=13) made 147 IgG responses to at least 70 proteins for genes overexpressed by HNSCC. Preliminary evaluation of the HNSCC peptidome against the results of MAP bead array identify antigens that are target of a humoral immune response. Additionally, tumor-reactive T cells from DPV-001 vaccinated patient recognize two partially HLA-matched HNSCC targets, but not a mis-matched target.ConclusionsRecent observations from our lab and others have correlated IgG Ab responses with T cell responses to epitopes of the same protein. Based on the data summarized above, we hypothesize that we have induced T cell responses against a broad spectrum of shared cancer antigens that are common among adenocarcinomas and squamous cell cancers. Our planned clinical trial will vaccinate and boost the induced responses by costimulation with anti-GITR and then sequence in delayed anti-PD-1 to relieve checkpoint inhibition. MAP bead arrays and the peptidome library generated above will be used to assess anti-cancer B and T cell responses.Trial RegistrationNCT04470024Ethics ApprovalThe original clinical trial was approved by the Providence Portland Medical Center IRB, approval # 13-046. The proposed clinical trial has not yet been reviewed by the IRB.

scholarly journals COVID-19 convalescents exhibit deficient humoral and T cell responses to variant of concern Spike antigens at 12 month post-infection

2021 ◽  
Author(s):  
Pablo Garcia-Valtanen ◽  
Christopher Martin Hope ◽  
Makutiro Ghislain Masavuli ◽  
Arthur Eng Lip Yeow ◽  
Harikrishnan Balachandran ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Post Infection ◽  
T Cell Responses ◽  
Memory B Cells ◽  
Pseudotyped Virus ◽  
Cell Responses ◽  
Specific Memory ◽  
Cell Functionality

Background The duration and magnitude of SARS-CoV-2 immunity after infection, especially with regard to the emergence of new variants of concern (VoC), remains unclear. Here, immune memory to primary infection and immunity to VoC was assessed in mild-COVID-19 convalescents one year after infection and in the absence of viral re-exposure or COVID-19 vaccination. Methods Serum and PBMC were collected from mild-COVID-19 convalescents at ~6 and 12 months after a COVID-19 positive PCR (n=43) and from healthy SARS-CoV-2-seronegative controls (n=15-40). Serum titers of RBD and Spike-specific Ig were quantified by ELISA. Virus neutralisation was assessed against homologous, pseudotyped virus and homologous and VoC live viruses. Frequencies of Spike and RBD-specific memory B cells were quantified by flow cytometry. Magnitude of memory T cell responses was quantified and phenotyped by activation-induced marker assay, while T cell functionality was assessed by intracellular cytokine staining using peptides specific to homologous Spike virus antigen and four VoC Spike antigens. Findings At 12 months after mild-COVID-19, >90% of convalescents remained seropositive for RBD-IgG and 88.9% had circulating RBD-specific memory B cells. Despite this, only 51.2% convalescents had serum neutralising activity against homologous live-SARS-CoV-2 virus, which decreased to 44.2% when tested against live B.1.1.7, 4.6% against B.1.351, 11.6% against P.1 and 16.2%, against B.1.617.2 VoC. Spike and non-Spike-specific T cells were detected in >50% of convalescents with frequency values higher for Spike antigen (95% CI, 0.29-0.68% in CD4+ and 0.11-0.35% in CD8+ T cells), compared to non-Spike antigens. Despite the high prevalence and maintenance of Spike-specific T cells in Spike 'high-responder' convalescents at 12 months, T cell functionality, measured by cytokine expression after stimulation with Spike epitopes corresponding to VoC was severely affected. Interpretations SARS-CoV-2 immunity is retained in a significant proportion of mild COVID-19 convalescents 12 months post-infection in the absence of re-exposure to the virus. Despite this, changes in the amino acid sequence of the Spike antigen that are present in current VoC result in virus evasion of neutralising antibodies, as well as evasion of functional T cell responses.

scholarly journals Human Papillomavirus Type 16 E7 Peptide-Directed CD8+ T Cells from Patients with Cervical Cancer Are Cross-Reactive with the Coronavirus NS2 Protein

2003 ◽  
Vol 77 (9) ◽  
pp. 5464-5474 ◽  
Author(s):  
Katja Nilges ◽  
Hanni Höhn ◽  
Henryk Pilch ◽  
Claudia Neukirch ◽  
Kirsten Freitag ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Immune Response ◽  
T Cells ◽  
Human Papillomavirus ◽  
T Cell ◽  
T Cell Responses ◽  
Cross Reactivity ◽  
Antiviral Immune Response ◽  
Human Papillomavirus Type 16 ◽  
Cell Responses

ABSTRACT Human papillomavirus type 16 (HPV16) E6 and E7 oncoproteins are required for cellular transformation and represent candidate targets for HPV-specific and major histocompatibility complex class I-restricted CD8+-T-cell responses in patients with cervical cancer. Recent evidence suggests that cross-reactivity represents the inherent nature of the T-cell repertoire. We identified HLA-A2 binding HPV16 E7 variant peptides from human, bacterial, or viral origin which are able to drive CD8+-T-cell responses directed against wild-type HPV16 E7 amino acid 11 to 19/20 (E711-19/20) epitope YMLDLQPET(T) in vitro. CD8+ T cells reacting to the HLA-A2-presented peptide from HPV16 E711-19(20) recognized also the HLA-A2 binding peptide TMLDIQPED (amino acids 52 to 60) from the human coronavirus OC43 NS2 gene product. Establishment of coronavirus NS2-specific, HLA-A2-restricted CD8+-T-cell clones and ex vivo analysis of HPV16 E7 specific T cells obtained by HLA-A2 tetramer-guided sorting from PBL or tumor-infiltrating lymphocytes obtained from patients with cervical cancer showed that cross-reactivity with HPV16 E711-19(20) and coronavirus NS252-60 represents a common feature of this antiviral immune response defined by cytokine production. Zero of 10 patients with carcinoma in situ neoplasia and 3 of 18 patients with cervical cancer showed ≥0.1% HPV16 E7-reactive T cells in CD8+ peripheral blood lymphocytes. In vivo priming with HPV16 was confirmed in patients with cervical cancer or preinvasive HPV16-positive lesions using HLA-A2 tetramer complexes loaded with the E6-derived epitope KLPQLCTEL. In contrast, we could not detect E6-reactive T cells in healthy individuals. These data imply that the measurement of the HPV16 E711-19(20) CD8+-T-cell response may reflect cross-reactivity with a common pathogen and that variant peptides may be employed to drive an effective cellular immune response against HPV.

Sign in / Sign up

Export Citation Format

Share Document