A5081446044- Immune Cell Function and Interaction
- HIV Research and Treatment
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- HIV/AIDS Research and Interventions
- Cytomegalovirus and herpesvirus research
- HIV/AIDS drug development and treatment
- Monoclonal and Polyclonal Antibodies Research
- interferon and immune responses
- HIV-related health complications and treatments
- Viral-associated cancers and disorders
- Hepatitis C virus research
- Diabetes and associated disorders
- Immune Response and Inflammation
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Vectors
- Hepatitis B Virus Studies
- Systemic Sclerosis and Related Diseases
- Systemic Lupus Erythematosus Research
- Herpesvirus Infections and Treatments
- Eosinophilic Disorders and Syndromes
- Immune cells in cancer
- Pharmacological Effects and Toxicity Studies
- Immune responses and vaccinations
- Animal Virus Infections Studies
Inserm
2015-2025
Immune Regulation (United Kingdom)
2025
Université de Bordeaux
2023-2025
Centre National de la Recherche Scientifique
2023-2025
Sorbonne Université
2013-2023
Centre d'Immunologie et des Maladies Infectieuses
2014-2023
Sorbonne Paris Cité
2019
Pitié-Salpêtrière Hospital
2009-2013
Immunité et Cancer
2013
UPMC Health System
2013
The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that responses specific for Gag and, particular, the immunodominant p24 epitope KK10 correlate with control HIV-1 replication histocompatibility leukocyte antigen (HLA)–B27 patients. To understand further nature cell–mediated antiviral efficacy, we performed a comprehensive study cells HLA-B27–restricted chronic based on use multiparametric flow cytometry together...
Abstract The cytotoxic potential of CD8+ T cells and NK plays a crucial role in the immune response to pathogens. Although vitro studies have reported that CD4+ are also able mediate perforin-mediated killing, vivo existence relevance been subject debate. Here we show population perforin+ is present circulation at low numbers healthy donors markedly expanded with chronic viral infections, particular HIV infection, all stages disease, including early primary infection. Ex analysis shows these...
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 self. It therefore postulated that EBV triggers SLE immunopathology, although the mechanism remains elusive. Here, we investigate whether frequent peaks of viral load in patients are a consequence dysfunctional anti-EBV CD8+ T cell responses. Both inactive active (n = 76 42, respectively), have...
Aging is associated with impaired vaccine efficacy and increased susceptibility to infectious malignant diseases. CD8+ T-cells are key players in the immune response against pathogens tumors. In aged mice, dwindling naïve T-cell compartment thought compromise induction of de novo responses, but no experimental evidence yet available humans. Here, we used an original vitro assay based on accelerated dendritic cell coculture system unfractioned peripheral blood mononuclear cells examine...
Pathogen recognition receptor (PRR) agonists are currently being developed and tested as adjuvants in various formulations to optimize the immunogenicity efficacy of vaccines. Using an original vitro approach prime naive precursors from unfractionated human peripheral blood mononuclear cells, we assessed influence cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), a ligand for stimulator interferon genes (STING), on induction antigen-specific CD8+ T cells. We found that...
Abstract Cytotoxic CD8+ T cells play a major role in the immune response against viruses. However, dynamics of cell responses during course human infection are not well understood. Using tetrameric complexes combination with range intracellular and extracellular markers, we present detailed analysis changes activation differentiation undergone by Ag-specific cells, relation to CD4+ responses, context infection: HIV-1. During primary HIV-1 infection, initial population HIV-specific is highly...
HIV-specific cytotoxic T lymphocytes (CTL) are important in controlling HIV replication, but the magnitude of CTL response does not predict clinical outcome. In four donors with delayed disease progression we identified Vβ13.2 cell receptors (TCRs) very similar and unusually long β-chain complementarity determining region 3 (CDR3) regions specific for immunodominant human histocompatibility leukocyte antigens (HLA)-B8–restricted immunodeficiency virus-1 (HIV-1) nef epitope, FLKEKGGL (FL8)....
As a first step towards HIV cure, we assessed strategy of antiretroviral therapy (ART) intensification followed by interleukin-7 (IL-7) used as an HIV-reactivating agent. A multicentre, randomized clinical trial included patients on suppressive ART with CD4 cell counts at least 350/μl and HIV-DNA between 10 1000 copies/10 peripheral blood mononuclear cells (PBMCs). After 8-week raltegravir maraviroc intensification, were to alone or 3 weekly IL-7 injections weeks 8, 9 10. The primary...
Background: Characterization of the intracellular biochemical processes that regulate generation and maintenance effector memory CD8+ T-cells from naïve precursors is essential for our understanding adaptive immune responses development immunotherapies. However, metabolic determinants antigen-driven activation differentiation remain poorly defined, especially in humans. Methods: We used a variety different approaches, including gene expression profiling measurements nutrient flux, to...
αβ CD8+, γδ, and NK lymphocytes are fundamental effector cells against viruses tumors. These can be divided into multiple subsets according to their phenotype. Based on progressive telomere attrition from naive late memory cells, human CD8+ T cell have been positioned along a pathway of differentiation, which is also considered as process lymphocyte aging or senescence. A similar categorization has not clearly established for γδ populations. Moreover, the distinction between these...
Aging is associated with functional deficits in the naive T cell compartment, which compromise generation of de novo immune responses against previously unencountered Ags. The mechanisms that underlie this phenomenon have nonetheless remained unclear. We found CD8+ cells elderly humans were prone to apoptosis and proliferated suboptimally response stimulation via TCR. These abnormalities dysregulated lipid metabolism under homeostatic conditions enhanced levels basal activation. Importantly,...
This analysis involves 22 patients with diagnosed symptomatic human immunodeficiency virus (HIV) infection. Neurologic symptoms were present in 11 patients, ranging from severe and persistent headache to clinical signs suggestive of meningitis. A strong correlation between neurological cerebrospinal fluid (CSF) viral load was found. The mean CSF HIV ribonucleic acid (RNA) level 4.12 log for 2.58 without ( P < .00001). Plasma alone does not correlate or predict central nervous system (CNS)...
The maintenance of effective immunity over time is dependent on the capacity hematopoietic stem cells (HSCs) to sustain pool immunocompetent mature cells. Decline immune competence with old age may from HSC defects, including reduced self-renewal potential and impaired lymphopoiesis, as suggested in murine models. To obtain further insights into aging-related alteration hematopoiesis, we performed a comprehensive study blood progenitor (HPCs) older humans. In elderly, HPCs present active...
CD8+ T cells are critical for immune protection against severe COVID-19 during acute infection with SARS-CoV-2. However, the induction of antiviral cell responses varies substantially among infected people, and a better understanding mechanisms that underlie such heterogeneity is required pandemic preparedness risk stratification. In this study, we analyzed SARS-CoV-2-specific CD4+ in relation to age, clinical status, inflammation patients primarily initial wave France or Japan. We found...
The type-I interferon family is well known for its critical role in innate immunity. It comprises several members, among which IFN-α2 and IFN-β are the most extensively studied, with important antiviral immune-modulatory functions. Recent findings linking autoantibodies against interferons to severe COVID-19 suggest a potential IFN-ω combating SARS-CoV-2 infection. However, little about human IFN-ω, as research on this has been conducted feline models. Here, we demonstrate that secreted at...
A majority of HIV-1-infected patients present a severe deficit in vitamin D, which predicts short-term mortality. Vitamin D is naturally synthesized hormone, with important immunomodulatory functions. In the general population, its has been associated increased markers inflammation. may therefore play role establishment elevated systemic immune activation, persists despite suppressive antiretroviral therapy (ART) HIV-infected patients, and predictive disease progression; supplementation be...
Abstract TLR agonists are currently being developed and tested as adjuvants in various formulations to optimize the immunogenicity efficacy of vaccines. The aim this study was evaluate immunostimulatory properties a novel compound incorporating covalently linked moieties designed stimulate both TLR2 TLR7. This dual TLR2/TLR7 agonist induced maturation dendritic cells primed substantial populations cytolytic highly polyfunctional effector CD8+ T vitro, safely potentiated immunogenic...
CD8+ T cells equipped with a full arsenal of antiviral effector functions are critical for effective immune control HIV-1. It has nonetheless remained unclear how best to elicit such potent cellular responses in the context immunotherapy or vaccination. HIV-2 been associated milder disease manifestations and more commonly elicits functionally replete virus-specific cell compared We aimed learn from this immunological dichotomy develop informed strategies that could enhance induction robust...
The mechanisms underlying non-progression in HIV-1 infection are not well understood; however, this state has been associated previously with strong HIV-1-specific CD8+ T cell responses and the preservation of proliferative CD4+ to antigens. Using a combination interferon-gamma (IFN-gamma) ELISpot assays tetramer staining, populations were quantified characterized untreated long-term HIV-1-infected non-progressors individuals slowly progressive disease, both relation responses, comparison...