A5082040256- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV Research and Treatment
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Diabetes and associated disorders
- Immune Response and Inflammation
- Herpesvirus Infections and Treatments
- Virus-based gene therapy research
- Glycosylation and Glycoproteins Research
- Immunodeficiency and Autoimmune Disorders
- SARS-CoV-2 and COVID-19 Research
- Cancer Immunotherapy and Biomarkers
- vaccines and immunoinformatics approaches
- Mycobacterium research and diagnosis
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- Protein purification and stability
- Viral-associated cancers and disorders
- HIV/AIDS drug development and treatment
- Single-cell and spatial transcriptomics
- Influenza Virus Research Studies
- RNA and protein synthesis mechanisms
University of Lausanne
2021-2025
National Institute of Allergy and Infectious Diseases
2015-2024
National Institutes of Health
2015-2024
Institut de Recherche Vaccinale
2022
Frequentis (Germany)
2022
Taipei Institute of Pathology
2021
University of Patras
2018
Drexel University
2004-2008
Institute for Molecular Medicine
2005-2007
Institute of Neuroimmunology of the Slovak Academy of Sciences
2006
Here, we report on the expression of programmed death (PD)-1 human virus-specific CD8+ T cells and effect manipulating signaling through PD-1 survival, proliferation, cytokine function these cells. was found to be low naive increased memory according antigen specificity. Memory specific for poorly controlled chronic persistent virus (HIV) more frequently expressed than well-controlled (cytomegalovirus) or acute (vaccinia) viruses. independent maturational markers not directly associated with...
CD4 T follicular helper (TFH) cells interact with and stimulate the generation of antigen-specific B cells. TFH cell interaction correlates production SIV-specific immunoglobulins. However, fate their participation in SIV-induced antibody is not well understood. We investigated phenotype, function, location, molecular signature rhesus macaques. Similar to human counterparts, macaques represented a heterogeneous population respect cytokine function. In highly differentiated subpopulation...
HIV-1 infection results in the progressive loss of CD4 T cells. In this study, we address how different pathogen-specific cells are affected by HIV and cellular parameters involved. We found striking differences depletion rates between to two common opportunistic pathogens, cytomegalovirus (CMV) Mycobacterium tuberculosis (MTB). CMV-specific persisted after infection, whereas MTB-specific were depleted rapidly. expressed a mature phenotype produced very little IL-2, but large amounts MIP-1β....
The interaction between follicular T helper cells (TFH) and B in the lymph nodes spleen has a major impact on development of antigen-specific cell responses during infection or vaccination. Recent studies described functional equivalent these among circulating CD4 cells, referred to as peripheral TFH cells. Here, we characterize phenotype vitro activity populations, well effect HIV populations. In co-culture experiments confirmed CXCR5+ from HIV-uninfected donors provide help more...
LN inflammation in chronic HIV is associated with accumulation of follicular CD8 T cells that could be redirected to kill infected cells.
Current paradigms of CD8 + T cell–mediated protection in HIV infection center almost exclusively on studies peripheral blood, which is thought to provide a window into immune activity at the predominant sites viral replication lymphoid tissues (LTs). Through extensive comparison thoracic duct lymph (TDL), and LTs different species, we show that many LT memory cells bear phenotypic, transcriptional, epigenetic signatures resident (T RMs ). Unlike their circulating counterparts blood or TDL,...
T follicular helper cells associate with development of highly mutated neutralizing antibodies against SHIV.
Elimination of lymphoid tissue reservoirs is a key component HIV eradication strategies. CD8+ T cells play critical role in control HIV, but their functional attributes lymph nodes (LNs) remain unclear. Here, we show that memory, follicular CXCR5+, and HIV-specific from LNs do not manifest the properties cytolytic cells. While frequency CXCR5+ was strongly inversely associated with peripheral viremia, this association dependent on Moreover, poor activity LN linked to compartmentalized...
Nearly all chronic human infections are associated with alterations in the memory B cell (MBC) compartment, including a large expansion of CD19hiT-bethi MBC peripheral blood HIV-infected individuals viremia. Despite their prevalence, it is unclear how these cells arise and whether they contribute to inefficiency antibody-mediated immunity infectious diseases. We addressed questions by characterizing T-bet-expressing lymph nodes (LN) identifying strong T-bet signature among HIV-specific poor...
Abstract The importance of chronic immune activation in progression to AIDS has been inferred by correlative studies HIV-infected individuals and nonhuman primate models SIV infection. Using the SIVmac251 macaque model, we directly address impact inhibiting CTLA-4, an immunoregulatory molecule expressed on activated T cells a subset regulatory cells. We found that CTLA-4 blockade significantly increased cell viral replication primary infection, particularly at mucosal sites, IDO expression...
Interleukin-15 (IL-15) in vitro treatment of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected individuals specifically enhances the function and survival HIV-specific CD8+ T cells, while vivo IL-15 mice preferentially expands memory cells. In this study, we investigated effect 9 SIVmac251-infected cynomolgus macaques (low dose IL-15, 10 microg/kg body weight, n = 3; high 100 microg/kg, control [saline], administered twice weekly for 4 weeks). induced...
Recent studies have revealed the critical role of programmed death-1 (PD-1) in exhaustion HIV- and SIV-specific CD8(+) T cells. In this study, we show that high expression PD-1 correlates with increased ex vivo spontaneous CD95/Fas-induced apoptosis, particularly "effector-memory" cell population from HIV(+) donors. High was linked to a proapoptotic phenotype characterized by low Bcl-2 IL7-R alpha, CD95/Fas mitochondrial mass. Expression CD57 differentially associated maturation status cells...
B cell follicles in secondary lymphoid tissues represent an immune privileged sanctuary for AIDS viruses, part because cytotoxic CD8 + T cells are mostly excluded from entering the that harbor infected follicular helper (T FH ) cells.We studied effects of native heterodimeric IL-15 (hetIL-15) treatment on uninfected rhesus macaques and had spontaneously controlled SHIV infection to low levels chronic viremia.hetIL-15 increased effector lymphocytes with high granzyme content blood, mucosal...
Despite the overwhelming benefits of antiretroviral therapy (ART) in curtailing viral load HIV-infected individuals, ART does not fully restore cellular and humoral immunity. individuals under show reduced responses to vaccination infections are unable mount an effective antiviral immune response upon cessation. Many factors contribute these defects, including persistent inflammation, especially lymphoid tissues, where T follicular helper (Tfh) cells instruct help B launch response. In this...
Vaccine responses vary by geographic location. We have previously described how HIV-associated inflammation leads to fibrosis of secondary lymph nodes (LNs) and T cell depletion. hypothesized that other infections may cause LN fibrosis, in a process similar seen HIV infection, which lead depletion affect vaccine responses. studied LNs individuals from Kampala, Uganda, before after yellow fever vaccination (YFV) found was infection. blunted antibody YFV correlated the amount loss cells,...
Abstract The role of costimulation has previously been confined to the very early stages CD8+ T cell response. In this study, we demonstrate requirement for CD27 during later phase, but not programming primary response influenza virus and reveal a novel mechanism action costimulation. signals, phase response, prevent apoptosis Ag-specific cells. Blocking CD27L (CD70) on days 6 8 after infection reduces number NP(366–374)-specific cells, increases their sensitivity CD95/Fas-mediated...
It is hypothesized that cancer stem cells arise either from normal or progenitor have gained the ability to self-renew.Here we determine whether mammary can be isolated by using antibodies been used for isolation of cells.We show BRCA1 mutant cell lines contained a subpopulation CD24+CD29+ CD24+CD49f+ exhibited increased proliferation and colony forming in vitro, enhanced tumor-forming vivo.The purified could differentiate reconstitute heterogeneity found parental when plated as...
LN follicles constitute major reservoir sites for HIV/SIV persistence. Cure strategies could benefit from the characterization of CD8+ T cells able to access and eliminate HIV-infected these areas. In this study, we provide a comprehensive analysis phenotype, frequency, localization, functionality follicular (fCD8+) in SIV-infected nonhuman primates. Although disorganization was factor, significant accumulation fCD8+ during chronic SIV infection also observed intact follicles, but only...
Broadly neutralizing antibodies (bNAbs) represent an alternative to drug therapy for the treatment of HIV-1 infection. Immunotherapy with single bNAbs often leads emergence escape variants, suggesting a potential benefit combination bNAb therapy. Here, trispecific reduces viremia 100- 1000-fold in viremic SHIV-infected macaques. After discontinuation, rebounds transiently and returns low levels, through CD8-mediated immune control. These viruses remain sensitive antibody, despite loss...
Abstract Anti-HIV-1 broadly neutralizing antibodies (bNAbs) have the dual potential of mediating virus neutralization and antiviral effector functions through their Fab Fc domains, respectively. So far, bNAbs with enhanced in vitro only been tested NHPs during chronic simian-HIV (SHIV) infection. Here, we investigate effects administering acute SHIV AD8-EO infection either wild-type (WT) or carrying S239D/I332E/A330L (DEL) mutation, which increases binding to FcγRs. Emergence plasma lymph...