A novel sensitive approach for frequency analysis of measles virus-specific memory T-lymphocytes in healthy adults with a childhood history of natural measles

Microbiology ◽  
2000 ◽  
Vol 81 (5) ◽  
pp. 1313-1319 ◽  
Author(s):  
Ralph Nanan ◽  
Andrea Rauch ◽  
Eckhart Kämpgen ◽  
Stefan Niewiesk ◽  
Hans Wolfgang Kreth
Keyword(s):  
T Cells ◽  
T Cell ◽  
Measles Virus ◽  
T Cell Responses ◽  
Healthy Adults ◽  
Cell Mediated Immunity ◽  
Median Frequency ◽  
Cell Responses ◽  
Specific Memory ◽  
History Of

Measles virus (MV), a single-stranded negative-sense RNA virus, is an important pathogen causing almost 1 million deaths annually. Acute MV infection induces immunity against disease throughout life. The immunological factors which are responsible for protection against measles are still poorly understood. However, T-cell-mediated immune responses seem to play a central role. The emergence of new single-cell methods for quantification of antigen-specific T-cells directly ex vivo has prompted us to measure frequencies of MV-specific memory T-cells. As an indicator for T-cell activation IFN-γ production was measured. PBMC were analysed by intracellular staining and ELISPOT assay after stimulation with MV-infected autologous B-lymphoblastoid cell lines or dendritic cells. T-cell responses were exclusively seen with PBMC from MV-seropositive healthy adults with a history of natural measles in childhood. The median frequency of MV-specific T-cells was 0·35% for CD3+CD4+ and 0·24% for the CD3+CD8+ T-cell subset. These frequencies are comparable with T-cell numbers reported by other investigators for persistent virus infections such as Epstein–Barr virus, cytomegalovirus or human immunodeficiency virus. Hence, this study illustrates that MV-specific CD4+ and CD8+ T-cells are readily detectable long after the acute infection, and thus are probably contributing to long-term immunity. Furthermore, this new approach allows efficient analysis of T-cell responses from small samples of blood and could therefore be a useful tool to further elucidate the role of cell-mediated immunity in measles as well as in other viral infections.

scholarly journals Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19

2020 ◽  
Author(s):  
Takuya Sekine ◽  
André Perez-Potti ◽  
Olga Rivera-Ballesteros ◽  
Kristoffer Strålin ◽  
Jean-Baptiste Gorin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Family Members ◽  
T Cell Responses ◽  
Clinical Markers ◽  
Cell Responses ◽  
Specific Memory ◽  
Cell Immunity ◽  
History Of

ABSTRACTSARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in a large cohort of unexposed individuals as well as exposed family members and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative family members and individuals with a history of asymptomatic or mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust memory T cell responses akin to those observed in the context of successful vaccines, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19 also in seronegative individuals.

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 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 Adenoviral vaccines promote protective tissue-resident memory T cell populations against cancer

2020 ◽  
Vol 8 (2) ◽  
pp. e001133
Author(s):  
Esmé TI van der Gracht ◽  
Mark JA Schoonderwoerd ◽  
Suzanne van Duikeren ◽  
Ayse N Yilmaz ◽  
Felix M Behr ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Adenoviral Vectors ◽  
Cell Populations ◽  
Dependent Manner ◽  
Cell Responses ◽  
Specific Memory ◽  
Tumor Protection

BackgroundAdenoviral vectors emerged as important platforms for cancer immunotherapy. Vaccination with adenoviral vectors is promising in this respect, however, their specific mechanisms of action are not fully understood. Here, we assessed the development and maintenance of vaccine-induced tumor-specific CD8+ T cells elicited upon immunization with adenoviral vectors.MethodsAdenoviral vaccine vectors encoding the full-length E7 protein from human papilloma virus (HPV) or the immunodominant epitope from E7 were generated, and mice were immunized intravenously with different quantities (107, 108 or 109 infectious units). The magnitude, kinetics and tumor protection capacity of the induced vaccine-specific T cell responses were evaluated.ResultsThe adenoviral vaccines elicited inflationary E7-specific memory CD8+ T cell responses in a dose-dependent manner. The magnitude of these vaccine-specific CD8+ T cells in the circulation related to the development of E7-specific CD8+ tissue-resident memory T (TRM) cells, which were maintained for months in multiple tissues after vaccination. The vaccine-specific CD8+ T cell responses conferred long-term protection against HPV-induced carcinomas in the skin and liver, and this protection required the induction and accumulation of CD8+ TRM cells. Moreover, the formation of CD8+ TRM cells could be enhanced by temporal targeting CD80/CD86 costimulatory interactions via CTLA-4 blockade early after immunization.ConclusionsTogether, these data show that adenoviral vector-induced CD8+ T cell inflation promotes protective TRM cell populations, and this can be enhanced by targeting CTLA-4.

scholarly journals The Breadth of Expandable Memory CD8+T Cells Inversely Correlates with Residual Viral Loads in HIV Elite Controllers

2015 ◽  
Vol 89 (21) ◽  
pp. 10735-10747 ◽  
Author(s):  
Zaza M. Ndhlovu ◽  
Eleni Stampouloglou ◽  
Kevin Cesa ◽  
Orestes Mavrothalassitis ◽  
Donna Marie Alvino ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Load ◽  
T Cell ◽  
T Lymphocytes ◽  
Hiv Infection ◽  
T Cell Responses ◽  
T Cell Response ◽  
Elite Controllers ◽  
Cell Responses ◽  
Specific Memory

ABSTRACTPrevious studies have shown that elite controllers with minimal effector T cell responses harbor a low-frequency, readily expandable, highly functional, and broadly directed memory population. Here, we interrogated thein vivorelevance of this cell population by investigating whether the breadth of expandable memory responses is associated with the magnitude of residual viremia in individuals achieving durable suppression of HIV infection. HIV-specific memory CD8+T cells were expanded by using autologous epitopic and variant peptides. Viral load was measured by an ultrasensitive single-copy PCR assay. Following expansion, controllers showed a greater increase in the overall breadth of Gag responses than did untreated progressors (P= 0.01) as well as treated progressors (P= 0.0003). Nef- and Env-specific memory cells expanded poorly for all groups, and their expanded breadths were indistinguishable among groups (P= 0.9 for Nef as determined by a Kruskal-Wallis test;P= 0.6 for Env as determined by a Kruskal-Wallis test). More importantly, we show that the breadth of expandable, previously undetectable Gag-specific responses was inversely correlated with residual viral load (r= −0.6;P= 0.009). Together, these data reveal a direct link between the abundance of Gag-specific expandable memory responses and prolonged maintenance of low-level viremia. Our studies highlight a CD8+T cell feature that would be desirable in a vaccine-induced T cell response.IMPORTANCEMany studies have shown that the rare ability of some individuals to control HIV infection in the absence of antiretroviral therapy appears to be heavily dependent upon special HIV-specific killer T lymphocytes that are able to inhibit viral replication. The identification of key features of these immune cells has the potential to inform rational HIV vaccine design. This study shows that a special subset of killer lymphocytes, known as central memory CD8+T lymphocytes, is at least partially involved in the durable control of HIV replication. HIV controllers maintain a large proportion of Gag-specific expandable memory CD8+T cells involved in ongoing viral suppression. These data suggest that induction of this cell subset by future HIV vaccines may be important for narrowing possible routes of rapid escape from vaccine-induced CD8+T cell responses.

scholarly journals Impact of Cytotoxic-T-Lymphocyte Memory Induction without Virus-Specific CD4+ T-Cell Help on Control of a Simian Immunodeficiency Virus Challenge in Rhesus Macaques

2009 ◽  
Vol 83 (18) ◽  
pp. 9339-9346 ◽  
Author(s):  
Tetsuo Tsukamoto ◽  
Akiko Takeda ◽  
Takuya Yamamoto ◽  
Hiroyuki Yamamoto ◽  
Miki Kawada ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Lymphocyte ◽  
Rhesus Macaques ◽  
T Cell Responses ◽  
Cell Responses ◽  
Specific Memory ◽  
Immunodeficiency Virus ◽  
Virus Exposure ◽  
T Cell Help

ABSTRACT Despite many efforts to develop AIDS vaccines eliciting virus-specific T-cell responses, whether induction of these memory T cells by vaccination before human immunodeficiency virus (HIV) exposure can actually contribute to effective T-cell responses postinfection remains unclear. In particular, induction of HIV-specific memory CD4+ T cells may increase the target cell pool for HIV infection because the virus preferentially infects HIV-specific CD4+ T cells. However, virus-specific CD4+ helper T-cell responses are thought to be important for functional CD8+ cytotoxic-T-lymphocyte (CTL) induction in HIV infection, and it has remained unknown whether HIV-specific memory CD8+ T cells induced by vaccination without HIV-specific CD4+ T-cell help can exert effective responses after virus exposure. Here we show the impact of CD8+ T-cell memory induction without virus-specific CD4+ T-cell help on the control of a simian immunodeficiency virus (SIV) challenge in rhesus macaques. We developed a prophylactic vaccine by using a Sendai virus (SeV) vector expressing a single SIV Gag241-249 CTL epitope fused with enhanced green fluorescent protein (EGFP). Vaccination resulted in induction of SeV-EGFP-specific CD4+ T-cell and Gag241-249-specific CD8+ T-cell responses. After a SIV challenge, the vaccinees showed dominant Gag241-249-specific CD8+ T-cell responses with higher effector memory frequencies in the acute phase and exhibited significantly reduced viral loads. These results demonstrate that virus-specific memory CD8+ T cells induced by vaccination without virus-specific CD4+ T-cell help could indeed facilitate SIV control after virus exposure, indicating the benefit of prophylactic vaccination eliciting virus-specific CTL memory with non-virus-specific CD4+ T-cell responses for HIV control.

scholarly journals Impaired Th17 immunity in recurrent C. difficile infection is ameliorated by fecal microbial transplantation

2020 ◽  
Author(s):  
Laura Cook ◽  
William D. Rees ◽  
May Q. Wong ◽  
Xiaojiao Wang ◽  
Hannah Peters ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
T Cell ◽  
Bowel Disease ◽  
Th17 Cells ◽  
T Cell Responses ◽  
Cell Mediated Immunity ◽  
Fecal Microbiota Transplant ◽  
Cell Responses ◽  
Inflammatory Bowel

ABSTRACTBackground & AimsClostridioides difficile is a leading cause of infectious diarrhea and an urgent antimicrobial resistant threat. Symptoms are caused by its toxins, TcdA and TcdB, with many patients developing recurrent C. difficile infection (CDI), requiring fecal microbiota transplant (FMT). Antibody levels have not been useful in predicting patient outcomes, which is an unmet need. We aimed to characterize T cell-mediated immunity to C. difficile toxins and assess how these responses were affected by FMT.MethodsWe obtained blood samples from patients with newly acquired CDI, recurrent CDI (with a subset receiving FMT), inflammatory bowel disease with no history of CDI, and healthy individuals (controls). Toxin-specific CD4+ T cell responses were analysed using a whole blood flow cytometry antigen-induced marker assay. Serum antibodies were measured by ELISA. Tetramer guided mapping was used to identify HLA-II-restricted TcdB epitopes and DNA was extracted from TcdB-specific CD4+ T cells for TCR repertoire analysis by Sanger sequencing.ResultsCD4+ T cell responses to C. difficile toxins were functionally diverse. Compared to controls, individuals with CDI, or inflammatory bowel disease had significantly higher frequencies of TcdB-specific CD4+ T cells. Subjects with recurrent CDI had reduced proportions of TcdB-specific CD4+ Th17 cells, FMT reversed this deficit and increased toxin-specific antibody production.ConclusionsThese data suggest that effective T cell immunity to C. difficile requires the development of Th17 cells. In addition, they show that an unknown aspect of the therapeutic effect of FMT may be enhanced T and B cell-mediated immunity to TcdB.GRAPHICAL ABSTRACT

scholarly journals Analysis of CD8+T cell response during the 2013–2016 Ebola epidemic in West Africa

2018 ◽  
Vol 115 (32) ◽  
pp. E7578-E7586 ◽  
Author(s):  
Saori Sakabe ◽  
Brian M. Sullivan ◽  
Jessica N. Hartnett ◽  
Refugio Robles-Sikisaka ◽  
Karthik Gangavarapu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
West Africa ◽  
Cell Response ◽  
Acute Infection ◽  
T Cell Responses ◽  
T Cell Response ◽  
Cell Mediated Immunity ◽  
T Cell Epitopes ◽  
Cell Responses

The recent Ebola epidemic exemplified the importance of understanding and controlling emerging infections. Despite the importance of T cells in clearing virus during acute infection, little is known about Ebola-specific CD8+T cell responses. We investigated immune responses of individuals infected with Ebola virus (EBOV) during the 2013–2016 West Africa epidemic in Sierra Leone, where the majority of the >28,000 EBOV disease (EVD) cases occurred. We examined T cell memory responses to seven of the eight Ebola proteins (GP, sGP, NP, VP24, VP30, VP35, and VP40) and associated HLA expression in survivors. Of the 30 subjects included in our analysis, CD8+T cells from 26 survivors responded to at least one EBOV antigen. A minority, 10 of 26 responders (38%), made CD8+T cell responses to the viral GP or sGP. In contrast, 25 of the 26 responders (96%) made response to viral NP, 77% to VP24 (20 of 26), 69% to VP40 (18 of 26), 42% (11 of 26) to VP35, with no response to VP30. Individuals making CD8+T cells to EBOV VP24, VP35, and VP40 also made CD8+T cells to NP, but rarely to GP. We identified 34 CD8+T cell epitopes for Ebola. Our data indicate the immunodominance of the EBOV NP-specific T cell response and suggest that its inclusion in a vaccine along with the EBOV GP would best mimic survivor responses and help boost cell-mediated immunity during vaccination.

scholarly journals Cytokines regulate the antigen-presenting characteristics of human circulating and tissue-resident intestinal ILCs

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Rao ◽  
Otto Strauss ◽  
Efthymia Kokkinou ◽  
Mélanie Bruchard ◽  
Kumar P. Tripathi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
T Cell Responses ◽  
Cancer Tissue ◽  
Dependent Manner ◽  
Cell Responses ◽  
Specific Memory ◽  
Hla Dr ◽  
Antigen Presenting

AbstractILCs and T helper cells have been shown to exert bi-directional regulation in mice. However, how crosstalk between ILCs and CD4+ T cells influences immune function in humans is unknown. Here we show that human intestinal ILCs co-localize with T cells in healthy and colorectal cancer tissue and display elevated HLA-DR expression in tumor and tumor-adjacent areas. Although mostly lacking co-stimulatory molecules ex vivo, intestinal and peripheral blood (PB) ILCs acquire antigen-presenting characteristics triggered by inflammasome-associated cytokines IL-1β and IL-18. IL-1β drives the expression of HLA-DR and co-stimulatory molecules on PB ILCs in an NF-κB-dependent manner, priming them as efficient inducers of cytomegalovirus-specific memory CD4+ T-cell responses. This effect is strongly inhibited by the anti-inflammatory cytokine TGF-β. Our results suggest that circulating and tissue-resident ILCs have the intrinsic capacity to respond to the immediate cytokine milieu and regulate local CD4+ T-cell responses, with potential implications for anti-tumor immunity and inflammation.

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