78 results on '"Sauce, Delphine"'
Search Results
2. Expression of immune checkpoint on subset of monocytes in old patients
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Royer, Luca, Chauvin, Manon, Dhiab, Jamila, Pedruzzi, Eric, Boddaert, Jacques, Sauce, Delphine, and Vallet, Hélène
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- 2023
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3. Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART.
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Gärtner, Kathleen, Domínguez-Rodríguez, Sara, Heaney, Judith, Gkouleli, Triantafylia, Grant, Paul, Dorgham, Karim, Sauce, Delphine, Soulie, Cathia, Busby, Eloise J., O'Sullivan, Denise M., Spyer, Moira, Botha, Johannes C., Angeles Muñoz-Fernandez, Maria, Tagarro, Alfredo, Cotugno, Nicola, Huggett, Jim F., Klein, Nigel, Palma, Paolo, Rojo Conejo, Pablo, and Foster, Caroline
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HIV-positive teenagers ,STRUCTURED treatment interruption ,HIV ,RNA ,BIOMARKERS - Abstract
Introduction: Initiation of antiretroviral treatment (ART) in patients early after HIV-infection and long-term suppression leads to low or undetectable levels of HIV RNA and cell-associated (CA) HIV DNA and RNA. Both CA-DNA and CA-RNA, overestimate the size of the HIV reservoir but CA-RNA as well as p24/cell-free viral RNA can be indicators of residual viral replication. This study describes HIV RNA amounts and levels of cytokines/soluble markers in 40 well-suppressed adolescents who initiated ART early in life and investigated which viral markers may be informative as endpoints in cure clinical trials within this population. Methods: Forty adolescents perinatally infected with HIV on suppressive ART for >5 years were enrolled in the CARMA study. HIV DNA and total or unspliced CARNA in PBMCs were analyzed by qPCR/RT-qPCR and dPCR/RT-dPCR. Cell-free HIV was determined using an ultrasensitive viral load (US-VL) assay. Plasma markers and p24 were analyzed by digital ELISA and correlations between total and unspliced HIV RNA and clinical markers, including age at ART, Western Blot score, levels of cytokines/inflammation markers or HIV CA-DNA, were tested. Results: CA-RNA was detected in two thirds of the participants and was comparable in RT-qPCR and RT-dPCR. Adolescents with undetectable CARNA showed significantly lower HIV DNA compared to individuals with detectable CA-RNA. Undetectable unspliced CA-RNA was positively associated with age at ART initiation and Western Blot score. We found that a higher concentration of TNF-a was predictive of higher CA-DNA and CA-RNA. Other clinical characteristics like US-VL, time to suppression, or percent CD4+ Tlymphocytes were not predictive of the CA-RNA in this cross-sectional study. Conclusions: Low CA-DNA after long-term suppressive ART is associated with lower CA-RNA, in concordance with other reports. Patients with low CA-RNA levels in combination with low CA-DNA and low Western Blot scores should be further investigated to characterize candidates for treatment interruption trials. Unspliced CA-RNA warrants further investigation as a marker that can be prioritized in paediatric clinical trials where the sample volume can be a significant limitation. [ABSTRACT FROM AUTHOR]
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- 2024
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4. IL-7 producing immunotherapy improves ex vivo T cell functions of immunosenescent patients, especially post hip fracture.
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Marton, Chrystel, Minaud, Alix, Coupet, Charles-Antoine, Chauvin, Manon, Dhiab, Jamila, Vallet, Hélène, Boddaert, Jacques, Kehrer, Nadine, Bastien, Bérangère, Inchauspe, Geneviève, Barraud, Luc, and Sauce, Delphine
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- 2023
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5. HIV disease progression despite suppression of viral replication is associated with exhaustion of lymphopoiesis
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Sauce, Delphine, Larsen, Martin, Fastenackels, Solène, Pauchard, Michèle, Ait-Mohand, Hocine, Schneider, Luminita, Guihot, Amélie, Boufassa, Faroudy, Zaunders, John, Iguertsira, Malika, Bailey, Michelle, Gorochov, Guy, Duvivier, Claudine, Carcelain, Guislaine, Kelleher, Anthony D., Simon, Anne, Meyer, Laurence, Costagliola, Dominique, Deeks, Steven G., Lambotte, Olivier, Autran, Brigitte, Hunt, Peter W., Katlama, Christine, and Appay, Victor
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- 2011
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6. Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity
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Almeida, Jorge R., Sauce, Delphine, Price, David A., Papagno, Laura, Shin, So Youn, Moris, Arnaud, Larsen, Martin, Pancino, Gianfranco, Douek, Daniel C., Autran, Brigitte, Sáez-Cirión, Asier, and Appay, Victor
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- 2009
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7. Increased carotid intima–media thickness is not associated with T-cell activation nor with cytomegalovirus in HIV-infected never-smoker patients
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Goulenok, Tiphaine, Boyd, Anders, Larsen, Martin, Fastenackels, Solène, Boccara, Franck, Meynard, Jean-Luc, Hadour, Nabila, Samri, Assia, Desvarieux, Moïse, Autran, Brigitte, Appay, Victor, Girard, Pierre-Marie, and Sauce, Delphine
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- 2015
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8. Vitamin D supplementation is associated with reduced immune activation levels in HIV-1-infected patients on suppressive antiretroviral therapy
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Fabre-Mersseman, Véronique, Tubiana, Roland, Papagno, Laura, Bayard, Charles, Briceno, Olivia, Fastenackels, Solène, Dudoit, Yasmine, Rostane, Hafeda, Salmon, Dominique, Costagliola, Dominique, Caby, Fabienne, Sauce, Delphine, Viard, Jean-Paul, and Appay, Victor
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- 2014
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9. Transcriptome of retrovirally transduced CD8 + lymphocytes: Influence of cell activation, transgene integration, and selection process
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Deschamps, Marina, Robinet, Eric, Certoux, Jean Marie, Mercier, Patricia, Sauce, Delphine, De Vos, John, Montcuquet, Nicolas, Bonyhadi, Mark, Rème, Thierry, Tiberghien, Pierre, and Ferrand, Christophe
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- 2008
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10. New advances in CMV and immunosenescence
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Sansoni, Paolo, Vescovini, Rosanna, Fagnoni, Francesco F., Akbar, Arne, Arens, Ramon, Chiu, Yen-Ling, Čičin-Šain, Luka, Dechanet-Merville, Julie, Derhovanessian, Evelyna, Ferrando-Martinez, Sara, Franceschi, Claudio, Frasca, Daniela, Fulöp, Tamas, Furman, David, Gkrania-Klotsas, Effrossyni, Goodrum, Felicia, Grubeck-Loebenstein, Beatrix, Hurme, Mikko, Kern, Florian, Lilleri, Daniele, López-Botet, Miguel, Maier, Andrea B., Marandu, Thomas, Marchant, Arnaud, Matheï, Catharina, Moss, Paul, Muntasell, Aura, Remmerswaal, Ester B.M., Riddell, Natalie E., Rothe, Kathrin, Sauce, Delphine, Shin, Eui-Cheol, Simanek, Amanda M., Smithey, Megan J., Söderberg-Nauclér, Cecilia, Solana, Rafael, Thomas, Paul G., van Lier, Rene, Pawelec, Graham, and Nikolich-Zugich, Janko
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- 2014
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11. Naive T cells: The crux of cellular immune aging?
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Appay, Victor and Sauce, Delphine
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- 2014
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12. Evidence of premature immune aging in patients thymectomized during early childhood
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Sauce, Delphine, Larsen, Martin, Fastenackels, Solene, Duperrier, Anne, Keller, Michael, Grubeck-Loebenstein, Beatrix, Ferrand, Christophe, Debre, Patrice, Sidi, Daniel, and Appay, Victor
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Young adults -- Health aspects -- Research ,Aging -- Research -- Health aspects ,Thymectomy -- Complications and side effects -- Health aspects -- Research ,Immunity -- Research -- Health aspects ,Health care industry - Abstract
While the thymus is known to be essential for the initial production of T cells during early life, its contribution to immune development remains a matter of debate. In fact, during cardiac surgery in newborns, the thymus is completely resected to enable better access to the heart to correct congenital heart defects, suggesting that it may be dispensable during childhood and adulthood. Here, we show that young adults thymectomized during early childhood exhibit an altered T cell compartment. Specifically, absolute [CD4.sup.+] and [CD8.sup.+] T cell counts were decreased, and these T cell populations showed substantial loss of naive cells and accumulation of oligoclonal memory cells. A subgroup of these young patients (22 years old) exhibited a particularly altered T cell profile that is usually seen in elderly individuals (more than 75 years old). This condition was directly related to CMV infection and the induction of strong CMV-specific T cell responses, which may exhaust the naive T cell pool in the absence of adequate T cell renewal from the thymus. Together, these marked immunological alterations are reminiscent of the immune risk phenotype, which is defined by a cluster of immune markers predictive of increased mortality in the elderly. Overall, our data highlight the importance of the thymus in maintaining the integrity of T cell immunity during adult life., Introduction The thymus is the major production site of T cells, whose stocks are built up during fetal and early postnatal life. However, its function diminishes after the first years [...]
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- 2009
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13. Clinical, Virological and Immunological Subphenotypes in a Cohort of Early Treated HIV-Infected Children.
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Domínguez-Rodríguez, Sara, Tagarro, Alfredo, Foster, Caroline, Palma, Paolo, Cotugno, Nicola, Zicari, Sonia, Ruggiero, Alessandra, de Rossi, Anita, Dalzini, Annalisa, Pahwa, Savita, Rinaldi, Stefano, Nastouli, Eleni, Marcelin, Anne-Geneviève, Dorgham, Karim, Sauce, Delphine, Gartner, Kathleen, Rossi, Paolo, Giaquinto, Carlo, and Rojo, Pablo
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HIV-positive children ,MONONUCLEAR leukocytes ,IMMUNE reconstitution inflammatory syndrome ,PEARSON correlation (Statistics) ,HIV - Abstract
Background: Identifying subphenotypes within heterogeneous diseases may have an impact in terms of therapeutic options. In this study, we aim to assess different subphenotypes in children living with human immunodeficiency virus (HIV-1), according to the clinical, virological, and immunological characteristics. Methods: We collected clinical and sociodemographic data, baseline viral load (VL), CD4 and CD8 count and percentage, age at initiation of ART, HIV DNA reservoir size in peripheral blood mononuclear cells (PBMCs), cell-associated RNA (CA-RNA), ultrasensitive VL, CD4 subsets (T effector CD25+, activated memory cells, Treg cells), humoral-specific HIV response (T-bet B cells), innate response (CD56dim natural killer (NK) cells, NKp46+, perforin), exhaustion markers (PD-1, PD-L1, DNAM), CD8 senescence, and biomarkers for T-lymphocyte thymic output (TREC) and endothelial activation (VCAM). The most informative variables were selected using an unsupervised lasso-type penalty selection for sparse clustering. Hierarchical clustering was performed using Pearson correlation as the distance metric and WARD.D2 as the clustering method. Internal validation was applied to select the best number of clusters. To compare the characteristics among clusters, boxplot and Kruskal Wallis test were assessed. Results: Three subphenotypes were discovered (cluster1: n=18, 45%; cluster2: n=11, 27.5%; cluster3: n=11, 27.5%). Patients in cluster1 were treated earlier, had higher baseline %CD4, low HIV reservoir size, low western blot score, higher TREC values, and lower VCAM values than the patients in the other clusters. In contrast, cluster3 was the less favorable. Patients were treated later and presented poorer outcomes with lower %CD4, and higher reservoir size, along with a higher percentage of CD8 immunosenescent cells, lower TREC, higher VCAM cytokine, and a higher %CD4 PD-1. Cluster2 was intermediate. Patients were like those of cluster1, but had lower levels of t-bet expression and higher HIV DNA reservoir size. Conclusions: Three HIV pediatric subphenotypes with different virological and immunological features were identified. The most favorable cluster was characterized by a higher rate of immune reconstitution and a slower disease progression, and the less favorable with more senescence and high reservoir size. In the near future therapeutic interventions for a path of a cure might be guided or supported by the different subphenotypes. [ABSTRACT FROM AUTHOR]
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- 2022
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14. Accelerated immune senescence and HIV-1 infection
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Appay, Victor, Almeida, Jorge R., Sauce, Delphine, Autran, Brigitte, and Papagno, Laura
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- 2007
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15. Mechanisms of immune aging in HIV.
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Chauvin, Manon and Sauce, Delphine
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OLDER people , *HIV infections , *HIV , *AGING , *VIRUS diseases - Abstract
Massive CD4+ T-cell depletion as well as sustained immune activation and inflammation are hallmarks of Human Immunodeficiency Virus (HIV)-1 infection. In recent years, an emerging concept draws an intriguing parallel between HIV-1 infection and aging. Indeed, many of the alterations that affect innate and adaptive immune subsets in HIV-infected individuals are reminiscent of the process of immune aging, characteristic of old age. These changes, of which the presumed cause is the systemic immune activation established in patients, likely participate in the immuno-incompetence described with HIV progression. With the success of antiretroviral therapy (ART), HIV-seropositive patients can now live for many years despite chronic viral infection. However, acquired immunodeficiency syndrome (AIDS)-related opportunistic infections have given way to chronic diseases as the leading cause of death since HIV infection. Therefore, the comparison between HIV-1 infected patients and uninfected elderly individuals goes beyond the sole onset of immunosenescence and extends to the deterioration of several physiological functions related to inflammation and systemic aging. In light of this observation, it is interesting to understand the precise link between immune activation and aging in HIV-1 infection to figure out how to best care for people living with HIV (PLWH). [ABSTRACT FROM AUTHOR]
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- 2022
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16. Transcriptome of retrovirally transduced CD8+ lymphocytes: Influence of cell activation, transgene integration, and selection process
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Deschamps, Marina, Robinet, Eric, Certoux, Jean Marie, Mercier, Patricia, Sauce, Delphine, De Vos, John, Montcuquet, Nicolas, Bonyhadi, Mark, Rème, Thierry, Tiberghien, Pierre, and Ferrand, Christophe
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- 2008
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17. LOX-1-Expressing Immature Neutrophils Identify Critically-Ill COVID-19 Patients at Risk of Thrombotic Complications.
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Combadière, Behazine, Adam, Lucille, Guillou, Noëlline, Quentric, Paul, Rosenbaum, Pierre, Dorgham, Karim, Bonduelle, Olivia, Parizot, Christophe, Sauce, Delphine, Mayaux, Julien, Luyt, Charles-Edouard, Boissonnas, Alexandre, Amoura, Zahir, Pourcher, Valérie, Miyara, Makoto, Gorochov, Guy, Guihot, Amélie, and Combadière, Christophe
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COVID-19 ,PROGNOSIS ,ADULT respiratory distress syndrome ,NEUTROPHILS ,CYTOKINE release syndrome - Abstract
Background: Lymphopenia and the neutrophil/lymphocyte ratio may have prognostic value in COVID-19 severity. Objective: We investigated neutrophil subsets and functions in blood and bronchoalveolar lavage (BAL) of COVID-19 patients on the basis of patients' clinical characteristics. Methods: We used a multiparametric cytometry profiling based to mature and immature neutrophil markers in 146 critical or severe COVID-19 patients. Results: The Discovery study (38 patients, first pandemic wave) showed that 80% of Intensive Care Unit (ICU) patients develop strong myelemia with CD10
− CD64+ immature neutrophils (ImNs). Cellular profiling revealed three distinct neutrophil subsets expressing either the lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), the interleukin-3 receptor alpha (CD123), or programmed death-ligand 1 (PD-L1) overrepresented in ICU patients compared to non-ICU patients. The proportion of LOX-1- or CD123-expressing ImNs is positively correlated with clinical severity, cytokine storm (IL-1β, IL-6, IL-8, TNFα), acute respiratory distress syndrome (ARDS), and thrombosis. BALs of patients with ARDS were highly enriched in LOX-1-expressing ImN subsets and in antimicrobial neutrophil factors. A validation study (118 patients, second pandemic wave) confirmed and strengthened the association of the proportion of ImN subsets with disease severity, invasive ventilation, and death. Only high proportions of LOX-1-expressing ImNs remained strongly associated with a high risk of severe thrombosis independently of the plasma antimicrobial neutrophil factors, suggesting an independent association of ImN markers with their functions. Conclusion: LOX-1-expressing ImNs may help identifying COVID-19 patients at high risk of severity and thrombosis complications. [ABSTRACT FROM AUTHOR]- Published
- 2021
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18. Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients.
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Chauvin, Manon, Larsen, Martin, Quirant, Bibiana, Quentric, Paul, Dorgham, Karim, Royer, Luca, Vallet, Hélène, Guihot, Amelie, Combadière, Béhazine, Combadière, Christophe, Barallat, Jaume, Mayaux, Julien, Luyt, Charles-Edouard, Mathian, Alexis, Amoura, Zahir, Boddaert, Jacques, Armestar, Fernando, Gorochov, Guy, Martinez-Caceres, Eva, and Sauce, Delphine
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COVID-19 ,NEOPTERIN ,TREATMENT effectiveness ,COVID-19 pandemic ,VIRUS diseases ,SARS-CoV-2 - Abstract
Highlights: Innate immune activation during Covid-19 infection is associated with pernicious clinical outcome. Background: Coronavirus disease 2019 (Covid-19) is a worldwide threat that has already caused more than 3 000 000 deaths. It is characterized by different patterns of disease evolution depending on host factors among which old-age and pre-existing comorbidities play a detrimental role. Previous coronavirus epidemics, notably SARS-CoV, were associated with increased serum neopterin levels, which can be interpreted as a sign of acute innate immunity in response to viral infection. Here we hypothesize that neopterin may serve as a biomarker of SARS-CoV-2 viral infection and Covid-19 disease severity. Methods: We measured neopterin blood levels by ELISA. Seric concentration was quantified from 256 healthy donors and 374 Covid-19 patients at hospital admission. Enrolled Covid-19 patients were all symptomatic and displayed a large spectrum of comorbidities. Patients were followed until disease resolution or death. Results: Severe and critically ill SARS-CoV-2 infected patients were characterized by a profound exacerbation of immune activation characterized by elevated neopterin blood levels. Systemic neopterin levels above 19nM stratified healthy individuals from Covid-19 patients with 87% specificity and 100% sensitivity. Moreover, systemic neopterin levels above 53nM differentiated non-survivors from survivors with 64% specificity and 100% sensitivity. Conclusion: We propose that neopterin concentration measured at arrival to hospital is a hallmark of severe Covid-19 and identifies a high-risk population of pernicious clinical outcome with a need for special medical care. [ABSTRACT FROM AUTHOR]
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- 2021
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19. Retrovirus-mediated gene transfer in polyclonal T cells results in lower apoptosis and enhanced ex vivo cell expansion of CMV-reactive CD8 T cells as compared with EBV-reactive CD8 T cells
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Sauce, Delphine, Rufer, Nathalie, Mercier, Patricia, Bodinier, Marie, Rémy-Martin, Jean-Paul, Duperrier, Anne, Ferrand, Christophe, Hervé, Patrick, Romero, Pedro, Lang, François, Tiberghien, Pierre, and Robinet, Eric
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- 2003
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20. Distinct cytokine profiles associated with COVID-19 severity and mortality.
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Dorgham, Karim, Quentric, Paul, Gökkaya, Mehmet, Marot, Stéphane, Parizot, Christophe, Sauce, Delphine, Guihot, Amélie, Luyt, Charles-Edouard, Schmidt, Matthieu, Mayaux, Julien, Beurton, Alexandra, Le Guennec, Loic, Demeret, Sophie, Ben Salah, Elyes, Mathian, Alexis, Yssel, Hans, Combadiere, Béhazine, Combadiere, Christophe, Traidl-Hoffmann, Claudia, and Burrel, Sonia
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Markedly elevated levels of proinflammatory cytokines and defective type-I interferon responses were reported in patients with coronavirus disease 2019 (COVID-19). We sought to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality. Cytokine concentrations and severe acute respiratory syndrome coronavirus 2 antigen were measured at hospital admission in serum of symptomatic patients with COVID-19 (N = 115), classified at hospitalization into 3 respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS), and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal-component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N = 86). At time of hospitalization, ECMO patients presented a dominant proinflammatory response with elevated levels of TNF-α, IL-6, IL-8, and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-β was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at 1 month was associated with higher levels of proinflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients, and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5% (risk ratio, 24.3; P <.0001). Severe acute respiratory syndrome coronavirus 2 antigen levels correlated with type-I interferon levels and were associated with mortality, but not with proinflammatory response or severity. Distinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality according to oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2021
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21. CMV and Immunosenescence: from basics to clinics
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Solana Rafael, Tarazona Raquel, Aiello Allison E, Akbar Arne N, Appay Victor, Beswick Mark, Bosch Jos A, Campos Carmen, Cantisán Sara, Cicin-Sain Luka, Derhovanessian Evelyna, Ferrando-Martínez Sara, Frasca Daniela, Fulöp Tamas, Govind Sheila, Grubeck-Loebenstein Beatrix, Hill Ann, Hurme Mikko, Kern Florian, Larbi Anis, López-Botet Miguel, Maier Andrea B, McElhaney Janet E, Moss Paul, Naumova Elissaveta, Nikolich-Zugich Janko, Pera Alejandra, Rector Jerrald L, Riddell Natalie, Sanchez-Correa Beatriz, Sansoni Paolo, Sauce Delphine, van Lier Rene, Wang George C, Wills Mark R, Zieliński Maciej, and Pawelec Graham
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Immunologic diseases. Allergy ,RC581-607 ,Geriatrics ,RC952-954.6 - Abstract
Abstract Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates “immunosenescence”. This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop.
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- 2012
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22. Report from the second cytomegalovirus and immunosenescence workshop
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Wills Mark, Akbar Arne, Beswick Mark, Bosch Jos A, Caruso Calogero, Colonna-Romano Giuseppina, Dutta Ambarish, Franceschi Claudio, Fulop Tamas, Gkrania-Klotsas Effrossyni, Goronzy Joerg, Griffiths Stephen J, Henson Sian M, Herndler-Brandstetter Dietmar, Hill Ann, Kern Florian, Klenerman Paul, Macallan Derek, Macaulay Richard, Maier Andrea B, Mason Gavin, Melzer David, Morgan Matthew, Moss Paul, Nikolich-Zugich Janko, Pachnio Annette, Riddell Natalie, Roberts Ryan, Sansoni Paolo, Sauce Delphine, Sinclair John, Solana Rafael, Strindhall Jan, Trzonkowski Piotr, van Lier Rene, Vescovini Rosanna, Wang George, Westendorp Rudi, and Pawelec Graham
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Immunologic diseases. Allergy ,RC581-607 ,Geriatrics ,RC952-954.6 - Abstract
Abstract The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion.
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- 2011
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23. Retrovirus-mediated gene transfer in primary T lymphocytes impairs their anti–Epstein-Barr virus potential through both culture-dependent and selection process–dependent mechanisms
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Sauce, Delphine, Bodinier, Marie, Garin, Marina, Petracca, Bruno, Tonnelier, Nicolas, Duperrier, Anne, Melo, Junia V., Apperley, Jane F., Ferrand, Christophe, Hervé, Patrick, Lang, François, Tiberghien, Pierre, and Robinet, Eric
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- 2002
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24. Immune activation and chronic inflammation: Is there an additional effect of HIV in a geriatric population?
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Sauce, Delphine, Pourcher, Valérie, Ferry, Tristan, Boddaert, Jacques, Slama, Laurence, and Allavena, Clotilde
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- 2021
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25. Hip Fracture Leads to Transitory Immune Imprint in Older Patients.
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Vallet, Héléne, Bayard, Charles, Lepetitcorps, Héléne, O'Hana, Jessica, Fastenackels, Soléne, Fali, Tinhinane, Cohen-Bittan, Judith, Khiami, Frédéric, Boddaert, Jacques, and Sauce, Delphine
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OLDER patients ,HIP fractures ,PROGRAMMED cell death 1 receptors ,HOSPITAL admission & discharge ,FUNCTIONAL analysis - Abstract
Background: Hip fracture (HF) is common in the geriatric population and is associated with a poor vital and functional prognosis which could be impacted by immunological changes. The objective here is to decipher immune changes occurring in the 1st days following HF and determine how phenotype, function, and regulation of innate and adaptive compartments adapt during acute stress event. Methods: We included HF patients, aged over 75 years. For each patient, blood samples were taken at five different timepoints: four in the perioperative period (day 0 to hospital discharge) and one at long term (6–12 months). Phenotypical and functional analysis were performed longitudinally on fresh blood or cryopreserved PBMCs. Clinical data were prospectively collected. Results: One-hundred HF patients and 60 age-matched controls were included. Innate compartment exhibits pro-inflammatory phenotypes (hyperleukocytosis, increase of CD14+ CD16+ proportion and CCR2 expression), maintaining its ability to produce pro-inflammatory cytokines. Adaptive compartment extends toward a transitory immunosuppressive profile (leucopenia) associated with an active T-cell proliferation. Furthermore, increases of LAG-3 and PD-1 and a decrease of 2-B4 expression are observed on T-cells, reinforcing their transitory suppressive status. Of note, these immune changes are transitory and sequential but may participate to a regulation loop necessary for homeostatic immune control at long term. Conclusion: HF is associated with several transitory immunological changes including pro-inflammatory phenotype in innate compartment and immunosuppressive profile in adaptive compartment. A comprehensive assessment of immune mechanisms implicated in the patient's prognosis after HF could pave the way to develop new immune therapeutics strategies. [ABSTRACT FROM AUTHOR]
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- 2020
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26. HIV-mediated immune aging in young adults infected perinatally or during childhood.
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Fastenackels, Solène, Sauce, Delphine, Vigouroux, Corinne, Avettand-Fènoël, Véronique, Bastard, Jean-Philippe, Fellahi, Soraya, Nailler, Laura, Arezes, Elisa, Rouzioux, Christine, Warszawski, Josiane, Viard, Jean Paul, Appay, Victor, and ANRS Co19 COVERTE Study Group
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- 2019
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27. The hallmarks of CMV-specific CD8 T-cell differentiation.
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van den Berg, Sara P. H., Pardieck, Iris N., Lanfermeijer, Josien, Sauce, Delphine, Klenerman, Paul, van Baarle, Debbie, and Arens, Ramon
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T cells ,ANTIBODY-dependent cell cytotoxicity ,TRANSCRIPTION factors ,LYMPHOCYTES - Abstract
Upon cytomegalovirus (CMV) infection, large T-cell responses are elicited that remain high or even increase over time, a phenomenon named memory T-cell inflation. Besides, the maintained robust T-cell response, CMV-specific T cells seem to have a distinctive phenotype, characterized by an advanced differentiation state. Here, we will review this "special" differentiation status by discussing the cellular phenotype based on the expression of CD45 isoforms, costimulatory, inhibitory and natural killer receptors, adhesion and lymphocyte homing molecules, transcription factors, cytokines and cytotoxic molecules. In addition, we focus on whether the differentiation state of CMV-specific CD8 T cells is unique in comparison with other chronic viruses and we will discuss the possible impact of factors such as antigen exposure and aging on the advanced differentiation status of CMV-specific CD8 T cells. [ABSTRACT FROM AUTHOR]
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- 2019
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28. The Oxygen Paradox, the French Paradox, and age-related diseases.
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Davies, Joanna, Cillard, Josiane, Friguet, Bertrand, Cadenas, Enrique, Cadet, Jean, Cayce, Rachael, Fishmann, Andrew, Liao, David, Bulteau, Anne-Laure, Derbré, Frédéric, Rébillard, Amélie, Burstein, Steven, Hirsch, Etienne, Kloner, Robert, Jakowec, Michael, Petzinger, Giselle, Sauce, Delphine, Sennlaub, Florian, Limon, Isabelle, and Ursini, Fulvio
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- 2017
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29. Assessing immune aging in HIV-infected patients.
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Appay, Victor and Sauce, Delphine
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HIV-positive persons , *IMMUNE response , *OLDER people , *DISEASE progression , *IMMUNOCOMPETENT cells - Abstract
Many of the alterations that affect innate and adaptive immune cell compartments in HIV-infected patients are reminiscent of the process of immune aging, characteristic of old age. These alterations define the immunological age of individuals and are likely to participate to the decline of immune competence with HIV disease progression. It is therefore important to characterize these changes, which point toward the accumulation of highly differentiated immunocompetent cells, associated with overall telomere length shortening, as well as understanding their etiology, especially related to the impact of chronic immune activation. Particular attention should be given to the exhaustion of primary immune resources, including haematopoietic progenitors and naïve cells, which holds the key for effective hematopoiesis and immune response induction, respectively. The alteration of these compartments during HIV infection certainly represents the foundation of the immune parallel with aging. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
30. A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness.
- Author
-
Souquette, Aisha, Frere, Justin, Smithey, Megan, Sauce, Delphine, and Thomas, Paul
- Published
- 2017
- Full Text
- View/download PDF
31. Reduced Oxidative Burst by Primed Neutrophils in the Elderly Individuals Is Associated With Increased Levels of the CD16bright/CD62Ldim Immunosuppressive Subset.
- Author
-
Sauce, Delphine, Yuan Dong, Campillo-Gimenez, Laure, Casulli, Sarah, Bayard, Charles, Autran, Brigitte, Boddaert, Jacques, Appay, Victor, Elbim, Carole, and Dong, Yuan
- Subjects
- *
NEUTROPHILS , *DISEASES in older people , *BACTERIAL diseases , *CYTOKINES , *INTERLEUKIN-6 , *PHAGOCYTOSIS , *ESCHERICHIA coli , *CELL receptors , *ANTIGENS , *GLYCOPROTEINS , *IMMUNOLOGICAL tolerance , *OXYGEN consumption , *PHYSIOLOGY , *CELL physiology - Abstract
The aim of our study was to analyze polymorphonuclear neutrophil (PMN) functions in elderly individuals compared with those in healthy young participants, directly in whole blood to avoid issues with data interpretation related to cell isolation procedures. Despite the presence of increased circulating levels of proinflammatory cytokines, resting PMNs from the elderly individuals were not activated as shown by normal CD62L and CD11b expression at the PMN surface and normal constitutive reactive oxygen species (ROS) production. However, suboptimal stimulation induced modulations of CD62L and CD11b expression, which positively correlated with the interleukin-6 circulating level, suggesting a possible in vivo preactivation of old PMNs by this cytokine. In addition, PMN phagocytosis of opsonized Escherichia Coli was decreased in elderly individuals. Furthermore, upon preincubation of elderly whole-blood samples with tumor necrosis factor-α or Toll Receptor agonists, we observed a reduced PMN oxidative burst in response to formyl peptides. Elderly participants also exhibited an increased percentage of the immunosuppressive CD16bright/CD62Ldim PMN subpopulation, which was characterized by a lower phagocytic index and a reduced ROS production compared with the CD16bright/CD62Lbright subset. Thus, the reduced phagocytosis and ROS production associated with an expansion of immunosuppressive CD16bright/CD62Ldim PMN subpopulation might be involved in the increased susceptibility to bacterial and fungal infections with old age. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
32. Aging of the immune system: Focus on inflammation and vaccination.
- Author
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Pinti, Marcello, Appay, Victor, Campisi, Judith, Frasca, Daniela, Fülöp, Tamas, Sauce, Delphine, Larbi, Anis, Weinberger, Birgit, and Cossarizza, Andrea
- Abstract
Major advances in preventing, delaying, or curing individual pathologies are responsible for an increasingly long life span in the developed parts of our planet, and indeed reaching eight to nine decades of life is nowadays extremely frequent. However, medical and sanitary advances have not prevented or delayed the underlying cause of the disparate pathologies occurring in the elderly: aging itself. The identification of the basis of the aging processes that drives the multiple pathologies and loss of function typical of older individuals is a major challenge in current aging research. Among the possible causes, an impairment of the immune system plays a major role, and indeed numerous studies have described immunological changes which occur with age. Far from the intention of being exhaustive, this review will focus on recent advances and views on the role that modifications of cell signalling and remodelling of the immune response play during human aging and longevity, paying particular attention to phenomena which are linked to the so called inflammaging process, such as dysregulation of innate immunity, altered T-cell or B-cell maturation and differentiation, as well as to the implications of immune aging for vaccination strategies in the elderly. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
33. Coordinated expansion of both memory T cells and NK cells in response to CMV infection in humans.
- Author
-
Bayard, Charles, Lepetitcorps, Hélène, Roux, Antoine, Larsen, Martin, Fastenackels, Solène, Salle, Virginie, Vieillard, Vincent, Marchant, Arnaud, Stern, Marc, Boddaert, Jacques, Bajolle, Fanny, Appay, Victor, and Sauce, Delphine
- Abstract
NK cells are key players in the fight against persistent viruses. Human cytomegalovirus (HCMV) infection is associated with the presence of a population of CD16
+ CD56dim NKG2C+ NK cells in both acutely and latently infected individuals. Here, we studied the nature of these terminally differentiated NK cells in different human populations infected with HCMV: healthy donors stratified by age, thymectomized individuals, pregnant women suffering from primary CMV infection, and lung transplant patients. Both CD16+ CD56dim NK- and CD8 T-cell phenotypes as well as functional capacities were determined and stratified according to age and/or CMV event. Similarly to T-cell responsiveness, we observe an accumulation over time of NKG2C+ NK cells, which preferentially expressed CD57. This accumulation is particularly prominent in elderly and amplified further by CMV infection. Latent HCMV infection (without replication) is sufficient for NKG2C+ CD57+ NK cells to persist in healthy individuals but is not necessarily required in old age. Collectively, the present work supports the emerging concept that CMV shapes both innate and adaptive immunity in humans. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
34. Reduced naïve CD8+ T-cell priming efficacy in elderly adults.
- Author
-
Briceño, Olivia, Lissina, Anna, Wanke, Kerstin, Afonso, Georgia, Braun, Amrei, Ragon, Kristanto, Miquel, Tiphaine, Gostick, Emma, Papagno, Laura, Stiasny, Karin, Price, David A., Mallone, Roberto, Sauce, Delphine, Karrer, Urs, and Appay, Victor
- Subjects
CD8 antigen ,T cells ,DRUG efficacy ,IMMUNE response ,LABORATORY mice - Abstract
Aging is associated with impaired vaccine efficacy and increased susceptibility to infectious and malignant diseases. CD8
+ T-cells are key players in the immune response against pathogens and tumors. In aged mice, the dwindling naïve CD8+ T-cell compartment is thought to compromise the induction of de novo immune responses, but no experimental evidence is yet available in humans. Here, we used an original in vitro assay based on an accelerated dendritic cell coculture system in unfractioned peripheral blood mononuclear cells to examine CD8+ T-cell priming efficacy in human volunteers. Using this approach, we report that old individuals consistently mount quantitatively and qualitatively impaired de novo CD8+ T-cell responses specific for a model antigen. Reduced CD8+ T-cell priming capacity in vitro was further associated with poor primary immune responsiveness in vivo. This immune deficit likely arises as a consequence of intrinsic cellular defects and a reduction in the size of the naïve CD8+ T-cell pool. Collectively, these findings provide new insights into the cellular immune insufficiencies that accompany human aging. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
35. Pathogen-Specific T Cell Polyfunctionality Is a Correlate of T Cell Efficacy and Immune Protection.
- Author
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Boyd, Anders, Almeida, Jorge R., Darrah, Patricia A., Sauce, Delphine, Seder, Robert A., Appay, Victor, Gorochov, Guy, and Larsen, Martin
- Subjects
T cells ,COMMUNICABLE disease treatment ,IN vitro studies ,CD8 antigen ,LEISHMANIA - Abstract
Introduction: Understanding the factors that delineate the efficacy of T cell responses towards pathogens is crucial for our ability to develop potent therapies against infectious diseases. Multidimensional evaluation of T cell functionality at the single-cell level enables exhaustive analysis of combinatorial functional properties, hence polyfunctionality. We have recently invented an algorithm that quantifies polyfunctionality, the Polyfunctionality Index (Larsen et al. PLoS One 2012). Here we demonstrate that quantitative assessment of T cell polyfunctionality correlates with T cell efficacy measured as the capacity to kill target cells in vitro and control infection in vivo. Methods: We employed the polyfunctionality index on two datasets selected for their unique ability to evaluate the polyfunctional imprint on T cell efficacy. 1) HIV-specific CD8
+ T cells and 2) Leishmania major-specific CD4+ T cells were analysed for their capacity to secrete multiple effector molecules, kill target cells and control infection. Briefly, employing the Polyfunctionality Index algorithm we determined the parameter estimates resulting in optimal correlation between T cell polyfunctionality and T cell efficacy. Results: T cell polyfunctionality is correlated with T cell efficacy measured as 1) target killing (r=0.807, P<0.0001) and 2) lesion size upon challenge with Leishmania major (r=-0.50, P=0.004). Contrary to an approach relying on the Polyfunctionality Index algorithm, quantitative evaluation of T cell polyfunctionality traditionally ignores the gradual contribution of more or less polyfunctional T cells. Indeed, comparing both approaches we show that optimal description of T cell efficacy is obtained when gradually integrating all levels of polyfunctionality in accordance with the Polyfunctionality Index. Conclusions: Our study presents a generalizable methodology to objectively evaluate the impact of polyfunctionality on T cell efficacy. We show that T cell polyfunctionality is a superior correlate of T cell efficacy both in vitro and in vivo as compared with response size. Therefore, future immunotherapies should aim to increase T cell polyfunctionality. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
36. The link between CD8⁺ T-cell antigen-sensitivity and HIV-suppressive capacity depends on HLA restriction, target epitope and viral isolate.
- Author
-
Lissina, Anna, Fastenackels, Solène, Inglesias, Maria C, Ladell, Kristin, McLaren, James E, Briceño, Olivia, Gostick, Emma, Papagno, Laura, Autran, Brigitte, Sauce, Delphine, Price, David A, Saez-Cirion, Asier, and Appay, Victor
- Published
- 2014
- Full Text
- View/download PDF
37. Monitoring cellular immune markers in HIV infection.
- Author
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Sauce, Delphine, Elbim, Carole, and Appay, Victor
- Published
- 2013
- Full Text
- View/download PDF
38. Lymphopenia-Driven Homeostatic Regulation of Naive T Cells in Elderly and Thymectomized Young Adults.
- Author
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Sauce, Delphine, Larsen, Martin, Fastenackels, Solène, Roux, Antoine, Gorochov, Guy, Katlama, Christine, Sidi, Daniel, Sibony-Prat, Joyce, and Appay, Victor
- Subjects
- *
LYMPHOPENIA , *HOMEOSTASIS , *T cells , *THYMECTOMY , *DISEASES in young adults , *OLDER patients , *IMMUNE response - Abstract
Reduced thymopoiesis and continuous mobilization of naive T cells into the effector-memory pool can lead to severe alterations of the naive T cell compartment. However, maintenance of the naive T cell population is essential to mount effective immune responses. Evidence of homeostatic regulation of naive T cells is currently debated in animal models. In humans, the situation remains unresolved, in particular with advanced age. In this study, we analyzed the CD4+ and CD8+ naive T cell compartments from elderly, young adults thymectomized during early childhood, and HIV-l-infected patients, which are characterized by T lymphocytopenia. We show a direct association between increased turnover and decreased frequency of naive T cells. Moreover, the IL-7-induced pathway was fully functional in naive T cells from elderly and young adults thymectomized during early childhood, who are characterized by elevated IL-7 plasma levels. Our findings support the establishment of homeostatic regulation of naive T cell proliferation in humans. This regulation is particularly active in lymphopenic hosts, such as elderly and thymec-tomized patients. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
39. Evaluating Cellular Polyfunctionality with a Novel Polyfunctionality Index.
- Author
-
Larsen, Martin, Sauce, Delphine, Arnaud, Laurent, Fastenackels, Solène, Appay, Victor, and Gorochov, Guy
- Subjects
- *
T cells , *MICE , *MEN , *CYTOKINES , *CHEMOKINES , *CYTOMETRY - Abstract
Functional evaluation of naturally occurring or vaccination-induced T cell responses in mice, men and monkeys has in recent years advanced from single-parameter (e.g. IFN-γ-secretion) to much more complex multidimensional measurements. Cosecretion of multiple functional molecules (such as cytokines and chemokines) at the single-cell level is now measurable due primarily to major advances in multiparametric flow cytometry. The very extensive and complex datasets generated by this technology raise the demand for proper analytical tools that enable the analysis of combinatorial functional properties of T cells, hence polyfunctionality. Presently, multidimensional functional measures are analysed either by evaluating all combinations of parameters individually or by summing frequencies of combinations that include the same number of simultaneous functions. Often these evaluations are visualized as pie charts. Whereas pie charts effectively represent and compare average polyfunctionality profiles of particular T cell subsets or patient groups, they do not document the degree or variation of polyfunctionality within a group nor does it allow more sophisticated statistical analysis. Here we propose a novel polyfunctionality index that numerically evaluates the degree and variation of polyfuntionality, and enable comparative and correlative parametric and non-parametric statistical tests. Moreover, it allows the usage of more advanced statistical approaches, such as cluster analysis. We believe that the polyfunctionality index will render polyfunctionality an appropriate end-point measure in future studies of T cell responsiveness. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
40. Exhausted Cytotoxic Control of Epstein-Barr Virus in Human Lupus.
- Author
-
Larsen, Martin, Sauce, Delphine, Deback, Claire, Arnaud, Laurent, Mathian, Alexis, Miyara, Makoto, Boutolleau, David, Parizot, Christophe, Dorgham, Karim, Papagno, Laura, Appay, Victor, Amoura, Zahir, and Gorochov, Guy
- Subjects
- *
SYSTEMIC lupus erythematosus , *EPSTEIN-Barr virus , *VIREMIA , *IMMUNOPATHOLOGY , *VIRAL load , *CYTOMEGALOVIRUSES - Abstract
Systemic Lupus Erythematosus (SLE) pathology has long been associated with an increased Epstein-Barr Virus (EBV) seropositivity, viremia and cross-reactive serum antibodies specific for both virus and self. It has therefore been postulated that EBV triggers SLE immunopathology, although the mechanism remains elusive. Here, we investigate whether frequent peaks of EBV viral load in SLE patients are a consequence of dysfunctional anti-EBV CD8+ T cell responses. Both inactive and active SLE patients (n = 76 and 42, respectively), have significantly elevated EBV viral loads (P = 0.003 and 0.002, respectively) compared to age- and sex-matched healthy controls (n = 29). Interestingly, less EBV-specific CD8 T cells are able to secrete multiple cytokines (IFN-γ, TNF-α, IL-2 and MIP-1β) in inactive and active SLE patients compared to controls (P = 0.0003 and 0.0084, respectively). Moreover, EBV-specific CD8 T cells are also less cytotoxic in SLE patients than in controls (CD107a expression: P = 0.0009, Granzyme B release: P = 0.0001). Importantly, cytomegalovirus (CMV)-specific responses were not found significantly altered in SLE patients. Furthermore, we demonstrate that EBV-specific CD8+ T cell impairment is a consequence of their Programmed Death 1 (PD-1) receptor up-regulation, as blocking this pathway reverses the dysfunctional phenotype. Finally, prospective monitoring of lupus patients revealed that disease flares precede EBV reactivation. In conclusion, EBV-specific CD8+ T cell responses in SLE patients are functionally impaired, but EBV reactivation appears to be an aggravating consequence rather than a cause of SLE immunopathology. We therefore propose that autoimmune B cell activation during flares drives frequent EBV reactivation, which contributes in a vicious circle to the perpetuation of immune activation in SLE patients. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
41. Multiparameter grouping delineates heterogeneous populations of human IL-17 and/or IL-22 T-cell producers that share antigen specificities with other T-cell subsets.
- Author
-
Larsen, Martin, Arnaud, Laurent, Hié, Miguel, Parizot, Christophe, Dorgham, Karim, Shoukry, Mohamed, Kemula, Mathilde, Barete, Stéphane, Derai, David, Sauce, Delphine, Amoura, Zahir, Pène, Jérôme, Yssel, Hans, and Gorochov, Guy
- Abstract
The ontogenic relationship between pro-inflammatory populations of interleukin-17 (IL-17A)- and/or IL-22-producing T cells and other T-cell subsets is currently unclear in humans. To appreciate T helper cell-lineage commitment, we combined cytokine production profiles of in vitro expanded T-cell clones with T-cell receptor (TCR) clonotypic signatures. Moreover, ex vivo cytokine production profiles at the single-cell level were analyzed using an original approach based on the hierarchical cluster analysis of multiparametric flow cytometry data. These combined approaches enabled the delineation of distinct functional T-cell subsets, including Th1, Th2, Tr1, Th17 cells and a highly polyfunctional IL-22-producing T-cell population. Cluster analysis highlighted that the IL-22-producing T-cell population should be considered independently from the Th17 and Th1 subsets, although it was more closely related to the former. In parallel, we observed extensive TCRαβ sharing across all five subsets defined. The strategy described here allows the objective definition of cellular subsets and an unbiased insight into their similarities. Together, our results underscore the ontogenic plasticity of CD4
+ T-cell progenitors, which can adopt a differentiation profile irrespective of antigen specificity. [ABSTRACT FROM AUTHOR]- Published
- 2011
- Full Text
- View/download PDF
42. Altered thymic activity in early life: how does it affect the immune system in young adults?
- Author
-
Sauce, Delphine and Appay, Victor
- Subjects
- *
YOUNG adults , *IMMUNE system , *THYMUS , *T cells , *IMMUNOSENESCENCE , *THYMECTOMY , *AGING - Abstract
The thymus is responsible for the maturation of lymphoid precursors into T cells, and is necessary to establish the T cell pool during prenatal and early postnatal life in humans. With the years, it undergoes a natural shrinking process, referred to as involution, suspected to be central in the decline of immune competence with aging, or immunosenescence. Here, we review the recent studies focusing on the immunological consequences of abnormal thymic development and thymectomy shortly after birth. These works highlight the importance of the thymic function in preserving immune efficacy throughout life, and provide insights into the development of immune aging. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
43. Upregulation of Interleukin 7 Receptor Alpha and Programmed Death 1 Marks an Epitope-Specific CD8+ T-Cell Response That Disappears following Primary Epstein-Barr Virus Infection.
- Author
-
Sauce, Delphine, Larsen, Martin, Abbott, Rachel J. M., Hislop, Andrew D., Leese, Alison M., Khan, Naeem, Papagno, Laura, Freeman, Gordon J., and Rickinson, Alan B.
- Subjects
- *
INTERLEUKINS , *T cells , *EPSTEIN-Barr virus , *EPITOPES , *ALPHA adrenoceptors - Abstract
In immunocompetent individuals, the stability of the herpesvirus-host balance limits opportunities to study the disappearance of a virus-specific CD8+ T-cell response. However, we noticed that in HLA-A*0201-positive infectious mononucleosis (IM) patients undergoing primary Epstein-Barr virus (EBV) infection, the initial CD8 response targets three EBV lytic antigen-derived epitopes, YVLDHLIVV (YVL), GLCTLVAML (GLC), and TLDYKPLSV (TLD), but only the YVL and GLC reactivities persist long-term; the TLD response disappears within 10 to 27 months. While present, TLD-specific cells remained largely indistinguishable from YVL and GLC reactivities in many phenotypic and functional respects but showed unique temporal changes in two markers of T-cell fate, interleukin 7 receptor alpha (IL-7Rα; CD127) and programmed death 1 (PD-1). Thus, following the antigen-driven downregulation of IL-7Rα seen on all populations in acute IM, in every case, the TLD-specific population recovered expression unusually quickly post-IM. As well, in four of six patients studied, TLD-specific cells showed very strong PD-1 upregulation in the last blood sample obtained before the cells' disappearance. Our data suggest that the disappearance of this individual epitope reactivity from an otherwise stable EBV-specific response (i) reflects a selective loss of cognate antigen restimulation (rather than of IL-7-dependent signals) and (ii) is immediately preceded, and perhaps mediated, by PD-1 upregulation to unprecedented levels. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
44. Cellular Responses to Viral Infection in Humans: Lessons from Epstein-Barr Virus.
- Author
-
Hislop, Andrew D., Taylor, Graham S., Sauce, Delphine, and Rickinson, Alan B.
- Subjects
EPSTEIN-Barr virus diseases ,CELLULAR immunity ,PROTEINS ,IMMUNE response ,MEMORY ,T cells - Abstract
Epstein-Barr virus (EBV) provides a useful model to study cellular immunity to a genetically stable, persistent human virus. Different sets of proteins expressed during EBV's lyric and cell transforming infections induce qualitatively different cellular immune responses. The factors governing immunodominance hierarchies and the biological effectiveness of these different responses are now being revealed. Analysis of infectious mononucleosis (IN[), a clinical syndrome that can arise during primary EBV infection, has allowed the evolution of the responses to be tracked over time, giving an understanding of the immune response kinetics and of those determinants affecting selection into memory. Furthermore, following IM, expression of the receptor for the homeostatic cytokine IL- 15 on NK and T cells is lost within these individuals. This experiment of nature provides a system to advance understanding of immunological homeostasis in humans, illustrating how data obtained from the study of EBV have wider significance to the immunological community. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
45. Influence de PD-1 sur la synapse immunologique Une facette de la régulation immunitaire?
- Author
-
Larsen, Martin, Appay, Victor, and Sauce, Delphine
- Published
- 2013
- Full Text
- View/download PDF
46. Serum Tryptophan-Derived Quinolinate and Indole-3-Acetate Are Associated With Carotid Intima-Media Thickness and its Evolution in HIV-Infected Treated Adults.
- Author
-
Boyd, Anders, Boccara, Franck, Meynard, Jean-Luc, Ichou, Farid, Bastard, Jean-Philippe, Fellahi, Soraya, Samri, Assia, Sauce, Delphine, Haddour, Nabila, Autran, Brigitte, Cohen, Ariel, Girard, Pierre-Marie, and Capeau, Jacqueline
- Subjects
CAROTID intima-media thickness ,CAROTID artery ,MASS spectrometry ,SERUM ,LIQUID chromatography - Abstract
Background HIV-infected individuals undergoing effective antiretroviral therapy (ART) present an increased risk of atherosclerotic cardiovascular disease. We identified serum metabolites associated with carotid intima-media thickness (c-IMT) and its evolution. Methods One hundred forty-three hydrophilic serum metabolites were measured by ultraperformance liquid chromatography coupled with high-resolution mass spectrometry in 49 HIV+ ART+, 48 HIV+ ART-naïve and 50 HIV-negative, age-matched, never-smoking male triads. Metabolites differentially altered between groups ("features") were defined as having a Benjamini-Hochberg-adjusted P value <.05 from a t test and >0.25 log
2 absolute mean fold change in metabolite levels. c-IMT was measured across 12 sites at inclusion in all individuals and at the carotid artery (cca) after a median of 5.1 years in 32 HIV+ ART+ individuals. The difference in c-IMT (cross-sectional analysis) and slope of cca-IMT regression/progression per year (longitudinal analysis) for each log10 (area) increase in metabolite level were estimated with linear regression. Results Compared with HIV-, metabolite features of HIV+ ART+ were increased N6,N6,N6-trimethyl-L-lysine and decreased ferulate and 5-hydroxy-L-tryptophan, whereas features of HIV+ ART-naïve were increased malate, kynurenine, 2-oxoglutarate, and indole-3-acetate and decreased succinate and 5-hydroxy-L-tryptophan. In HIV+ ART+ individuals, quinolinate and/or indole-3-acetate were positively associated with c-IMT (P < .03), cca-IMT (P < .03), and cca-IMT progression (P < .008). These associations were not observed in HIV+ ART-naïve or HIV-negative individuals. In HIV+ ART+ individuals, the metabolites xanthosine and uridine, from nucleotide metabolism, and g-butyrobetaine, from lysine/dietary choline degradation, were also positively or negatively associated with c-IMT and/or cca-IMT (all P < .01), but not its evolution. Conclusions In these highly selected HIV-positive ART-controlled males, 2 novel metabolites derived from tryptophan catabolism, indole-3-acetate and quinolinate, were associated with c-IMT and its progression. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
47. HIV-specific Th2 and Th17 responses predict HIV vaccine protection efficacy.
- Author
-
Sauce, Delphine, Gorochov, Guy, and Larsen, Martin
- Published
- 2016
- Full Text
- View/download PDF
48. Correction: Pathogen-Specific T Cell Polyfunctionality Is a Correlate of T Cell Efficacy and Immune Protection.
- Author
-
Boyd, Anders, Almeida, Jorge R., Darrah, Patricia A., Sauce, Delphine, Seder, Robert A., Appay, Victor, Gorochov, Guy, and Larsen, Martin
- Subjects
PATHOGENIC microorganisms ,IMMUNOLOGIC diseases ,DRUG efficacy ,MEDICAL research ,DATA analysis ,PREVENTION - Published
- 2015
- Full Text
- View/download PDF
49. Impact of stress on aged immune system compartments: Overview from fundamental to clinical data.
- Author
-
Fali, Tinhinane, Vallet, Hélène, and Sauce, Delphine
- Subjects
- *
LIFE expectancy , *DISEASES in older people , *DISEASES , *PSYCHOLOGICAL stress , *IMMUNE system , *IMMUNOGLOBULINS , *IMMUNE response - Abstract
Life expectancy is continuously increasing due to major progress in preventing, delaying or curing various pathologies normally encountered in old age. However, both scientific and medical advances are still required to understand underlying cause of the disparate comorbidities occurrence with aging. In one hand, aging profoundly impairs the immune system; it is characterized by many changes in haematopoiesis, adaptive and innate systems, associated with pro-inflammatory environment. In another hand, stressful events (acute or chronic) can also impact the immune system through the secretion of hormones, which are also altered with aging. The field of psychoneuroimmunology is now providing evidences that in acute medical conditions, elderly people are not equal in their responses to stressors depending on many extrinsic and intrinsic factors. These parameters could interfere with elderly's ability to mount an effective immune response. The objective of this review is to provide an overview of the literature (from fundamental to clinical observations) to draw a parallel between immune dysregulation caused by stress or by aging. Understanding this entanglement could enable us to target fundamental age-related pathways and thus open new avenues in improving both lifespan and health span. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
50. Phenotypic and Functional Differences between Human Herpesvirus 6- and Human Cytomegalovirus-Specific T Cells.
- Author
-
Fastenackels, Solène, Bayard, Charles, Larsen, Martin, Magnier, Philippe, Bonnafous, Pascale, Seddiki, Nabila, Appay, Victor, Gautheret-Dejean, Agnès, and Sauce, Delphine
- Subjects
- *
HUMAN cytomegalovirus , *HERPESVIRUSES , *HUMAN T cells , *T cells , *BLOOD cells - Abstract
Human herpesvirus 6 (HHV-6) infects >90% of the population and establishes a latent infection with asymptomatic episodes of reactivation. However, HHV-6 reactivation is associated with morbidity and sometimes mortality in immunocompromised patients. To date, control of the virus in healthy virus carriers and the failure to control it in patients with disease remain poorly understood. In particular, knowledge of HHV-6-specific T-cell responses is limited. Here, we characterized HHV-6A- and HHV-6Bspecific CD4+ and CD8+ T-cell responses from peripheral blood mononuclear cells (PBMCs) of healthy donors. We studied the phenotype of effector HHV-6-specific T cells ex vivo, as well as of induced specific suppressive regulatory CD4+ T cells in vitro post-stimulation, in comparison to human cytomegalovirus (HCMV) responses. Compared to that for HCMV, we show that ex vivo T-cell reactivity in peripheral blood is detectable but at very low frequency, both for HHV-6A and -6B viruses. Interestingly, the phenotype of the specific T cells also differs between the viruses. HHV-6A- and HHV-6B-specific CD4+ T lymphocytes are less differentiated than HCMV-specific T cells. Furthermore, we show a higher frequency of HHV-6-specific suppressive regulatory T cells (eTregs) than HCMV-specific eTregs in coinfected individuals. Despite the strong similarity of HHV-6 and HCMV from a virologic point of view, we observed immunological differences, particularly in relation to the frequency and phenotype of effector/memory and regulatory virus-specific T cells. This suggests that different immune factors are solicited in the control of HHV-6 infection than in that of HCMV infection. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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