A5030160770- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- HIV Research and Treatment
- COVID-19 Clinical Research Studies
- vaccines and immunoinformatics approaches
- Poxvirus research and outbreaks
- Herpesvirus Infections and Treatments
- CAR-T cell therapy research
- Immune responses and vaccinations
- Virus-based gene therapy research
- Long-Term Effects of COVID-19
- Monoclonal and Polyclonal Antibodies Research
- Viral gastroenteritis research and epidemiology
- Cytomegalovirus and herpesvirus research
- Immunodeficiency and Autoimmune Disorders
- Bacillus and Francisella bacterial research
- Vaccine Coverage and Hesitancy
- Immune Response and Inflammation
- Viral Infections and Immunology Research
- Single-cell and spatial transcriptomics
- COVID-19 epidemiological studies
- Viral Infections and Outbreaks Research
- Cancer Genomics and Diagnostics
La Jolla Institute for Immunology
2016-2025
University of California, San Diego
2016-2025
Scripps Research Institute
2012-2024
Scripps Institution of Oceanography
2016-2024
Center for Global Health
2024
Buckinghamshire Healthcare NHS Trust
2024
International AIDS Vaccine Initiative
2013-2023
La Jolla Alcohol Research
2022-2023
Scripps Health
2020-2022
University of California System
2022
Understanding immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics and vaccines assessing the likely future course of COVID-19 pandemic. We analyzed multiple compartments circulating SARS-CoV-2 in 254 samples from 188 cases, including 43 at ≥6 months after infection. Immunoglobulin G (IgG) spike protein was relatively stable over 6+ months. Spike-specific B cells were more abundant 6 than 1 month symptom onset. SARS-CoV-2-specific CD4
Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches adaptive immunity at level SARS-CoV-2-specific CD4
Effective B cell-mediated immunity and antibody responses often require help from CD4+ T cells. It is thought that a distinct effector cell subset, called follicular helper cells (T(FH)), provides this help; however, the molecular requirements for T(FH) differentiation are unknown. We found expression of transcription factor Bcl6 in both necessary sufficient vivo to mice. In contrast, Blimp-1, an antagonist Bcl6, inhibits help, thereby preventing germinal center responses. These findings...
Many unknowns exist about human immune responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. SARS-CoV-2-reactive CD4
The nature of follicular helper CD4+ T (Tfh) cell differentiation remains controversial, including the minimal signals required for Tfh and time at which occurs. Here we determine that development initiates immediately during dendritic (DC) priming in vivo. We demonstrate inducible costimulator (ICOS) provides a critical early signal to induce transcription factor Bcl6, Bcl6 then induces CXCR5, canonical feature cells. Strikingly, bifurcation between effector Th cells was measurable by...
RNA viruses evolve rapidly. One source of this ability to rapidly change is the apparently high mutation frequency in virus populations. A a central tenet quasispecies theory. corollary theory postulates that, given their frequency, animal may be susceptible error catastrophe, where they undergo sharp drop viability after modest increase frequency. We recently showed that important broad-spectrum antiviral drug ribavirin (currently used treat hepatitis C infections, among others) an mutagen,...
Abstract Memory B cells are a central component of humoral immunity, and yet little is known about their longevity in humans. Immune memory after smallpox vaccination (DryVax) valuable benchmark for understanding the cell absence re-exposure to Ag. In this study, we demonstrate that vaccine-specific last >50 years immunized individuals. Virus-specific initially declined postimmunization, but then reached plateau ∼10-fold lower than peak were stably maintained at frequency ∼0.1% total...
The emergence of SARS-CoV-2 variants with evidence antibody escape highlight the importance addressing whether total CD4
A defining characteristic of persistent viral infections is the loss and functional inactivation antiviral effector T cells, which prevents clearance. Interleukin-10 (IL-10) suppresses cellular immune responses by modulating function cells antigen-presenting cells. In this paper, we report that IL-10 production drastically increased in mice persistently infected with lymphocytic choriomeningitis virus. vivo blockade receptor (IL-10R) a neutralizing antibody resulted rapid resolution...
Cytokines are important modulators of lymphocytes, and both interleukin-21 (IL-21) IL-6 have proposed roles in T follicular helper (Tfh) differentiation, directly act on B cells. Here we investigated the absence alone, IL-21 or combined lack Tfh differentiation development cell immunity vivo. C57BL/6 IL-21(-/-) mice were treated with a neutralizing monoclonal antibody against throughout course an acute viral infection (lymphocytic choriomeningitis virus, LCMV). The resulted reduced Bcl6...
Follicular helper T cells (TFH cells) constitute the CD4+ cell subset that is specialized to provide help germinal center (GC) B and, consequently, mediate development of long-lived humoral immunity. TFH differentiation driven by transcription factor Bcl6, and recent studies have identified cytokine cell–cell signals drive Bcl6 expression. However, although dysregulation associated with several major autoimmune diseases, mechanisms underlying negative regulation are poorly understood. In...