Chairs
Dr Deepak Rao, Harvard University, USA
Dr Deepak Rao, Harvard University, USA
Dr Rao is a rheumatologist and immunologist at Brigham and Women’s Hospital and Assistant Professor of Medicine at Harvard Medical School. He serves are co-director of the Human Immunology Center and scientific co-director of the Single Cell Genomics Core at BWH. His work focuses on identifying the immune cell phenotypes and pathways that characterize distinct autoimmune diseases. Using high dimensional analyses including mass cytometry and RNA-seq of samples from patients with rheumatoid arthritis and lupus, his group described a population of ‘T peripheral helper’ cells that is pathologically expanded in multiple autoantibody-associated conditions. His ongoing work focuses on defining regulators of human Tph and Tfh cell function, and utilizing Tph and Tfh cell phenotypes as clinical metrics of autoimmune activation. He has received a Career Award for Medical Scientists from the Burroughs Welcome Fund and a Clinical Scientist Development Award from the Doris Duke Charitable Foundation to support these efforts.
13:30-13:55
Talk 4: Follicular regulatory T cells in rheumatic diseases
Professor Luis Graca, Instituto de Medicina Molecular, Faculdade de Medicin, Universidade de Lisboa, Portugal
Abstract
Germinal centres (GC) are anatomic structures where B cells undergo affinity maturation leading to production of high-affinity antibodies. The balance between T follicular helper (Tfh) and regulatory (Tfr) cells is critical for adequate control of GC responses. The study of human Tfh and Tfr cells’ development has been hampered due to the lack of in vitro assays reproducing the in vivo biology, along with difficult access to healthy human lymphoid tissues. We investigated the maturation of human Tfh and Tfr cells isolated from different human tissues using single cell transcriptomics, as well as samples from patients with rheumatic diseases. This way, it became possible to reconstruct the normal maturation trajectory for human Tfh and Tfr cells, and to uncover differences in their differentiation that are associated with autoimmune rheumatic diseases.
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Professor Luis Graca, Instituto de Medicina Molecular, Faculdade de Medicin, Universidade de Lisboa, Portugal
Professor Luis Graca, Instituto de Medicina Molecular, Faculdade de Medicin, Universidade de Lisboa, Portugal
Luis Graca has an MD from the University of Lisbon, Portugal; and a PhD in transplant immunology from the University of Oxford, UK. He developed his post-doctoral research first in Oxford and later at the Institute for Child Health Research, in Perth, Australia. He is currently Professor of Immunology at the University of Lisbon Medical School, directing a research group in Cellular Immunology at the Instituto de Medicina Molecular.
His most significant scientific contributions have been related with the field of transplantation and autoimmunity. Graca has worked on strategies to overcome transplant rejection, as well as in the induction of immune tolerance in autoimmunity and allergy. Among these topics he has been especially interested in the biology of different types of regulatory T cells, namely T follicular regulatory cells – a cell type he co-discovered.
Graca is President of the Sociedade das Ciências Médicas de Lisboa, the oldest medical society in Europe (founded 1822) and past-president of the Portuguese Society for Immunology.
13:55-14:20
Talk 5: Ageing and the response to vaccination
Dr Michelle Linterman, Babraham Institute Cambridge, UK
Abstract
Ageing dramatically affects the function of the immune system, resulting in increased susceptibility to infections and increased infection-related morbidity and mortality in older members of our communities. Notably, there is already an established intervention that can prevent a range of potentially life-threatening infections - vaccination. It has been observed, however, that older individuals often do not generate protective immunity after vaccination. The reasons for this are poorly understood, but it is clear that this leads to an increased prevalence of preventable disease in older people, even when good immunisation programmes are in place. At the heart of the immune response to vaccination is the germinal centre (GC) – a dynamic structure that forms in secondary lymphoid tissues after immunisation, and produces long-lived plasma cells, which secrete antibodies that block pathogens from establishing an infection, and memory B cells. A defining property of the GC is the collaboration of multiple cell types: proliferating B cells, T follicular helper cells (Tfh), T follicular regulatory cells (Tfr) and follicular dendritic cells to produce effector B cells of higher quality. With age, the magnitude of the GC response decreases resulting in impaired production of plasma cells, lower serum antibody levels and consequently, decreased protection against subsequent infection. Our research aims to understand how ageing affects the multiple cell types that participate in the GC response, and how we could mitigate the age-dependent changes with the goal of enhancing vaccine efficacy in older persons.
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Dr Michelle Linterman, Babraham Institute Cambridge, UK
Dr Michelle Linterman, Babraham Institute Cambridge, UK
Michelle Linterman is Group Leader at the Babraham Institute and a Fellow of Churchill College, Cambridge. Her laboratory’s principle research focus is on how different cell types collaborate in the germinal centre to generate a robust antibody response following vaccination. Michelle received her PhD in Immunology from the Australian National University in Canberra, under the supervison of Professor Carola Vinuesa. Then, Michelle was a Post-doctoral research associate with Professor Ken Smith at the University of Cambridge.
14:20-14:40
Additional Q&A for talks 4&5 and discussion
14:50-15:15
Talk 6: Regulation of CD11c+ T-bet+ B cells in autoimmunity
Professor Alessandra Pernis, Hospital for Special Surgery, Weill Cornell Medicine, USA
Abstract
Studies in aging mice have recently identified a B cell subset, termed ABCs (Age/Autoimmune-associated B cells), which exhibits a unique phenotype and preferentially expands in females with age. In addition to classical B cell markers, ABCs also express T-bet and myeloid markers like CD11c hence these cells are also known as CD11c+ T-bet+ B cells. Formation of ABCs is promoted by a combination of signals that include TLR7 engagement and cytokines like IFN- and IL-21. Both murine and human studies have shown a close association between aberrant accumulation of ABCs and the development of autoimmunity. In particular, ABCs expand prematurely in murine lupus and produce pathogenic autoantibodies. Furthermore, expansion of human ABC-like cells (also known as Double Negative=DN or DN2 B cells) has been observed in SLE patients where they have been shown to be major producers of autoAbs and to correlate with disease activity and clinical manifestations. Here I will discuss work from our lab on the molecular pathways that regulate the expansion, function, and differentiation of ABCs in autoimmune settings.
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Professor Alessandra Pernis, Hospital for Special Surgery, Weill Cornell Medicine, USA
Professor Alessandra Pernis, Hospital for Special Surgery, Weill Cornell Medicine, USA
Dr Pernis is a Senior Scientist and the Peter Jay Sharp Chair in Lupus Research at the Hospital for Special Surgery. She is a Professor of Medicine at Weill Cornell Medical College and a member of the HSS-Cornell-MSKCC Tri-institutional Immunology and Microbial Pathogenesis program. She employs both comparative models and translational approaches to delineate the molecular networks responsible for lymphocyte dysfunction in Systemic Lupus Erythematosus and autoimmune diseases. Her recent studies have demonstrated that members of the Interferon Regulatory Factor family of transcription factors control the generation of CD11c+T-bet+ B cells, also known as Age-associated B cells, and that dysregulation of ABCs can lead to lupus.
15:15-15:40
Talk 7: Maintenance of Tfh cell identity and its impact on GCs
Professor Dirk Baumjohann, University Hospital Bonn, Germany
Abstract
T follicular helper (Tfh) cells are crucial for the establishment of germinal centers (GCs) and potent antibody responses that are elicited during infection and vaccination. Despite their importance for humoral immunity, the T cell-intrinsic factors that are required for the maintenance of already established Tfh cells and GCs remain largely unknown.Temporally guided, tamoxifen-inducible CD4+ T cell-specific gene ablation was used to dissect the contributions of CXCR5, Bcl6, and mature miRNAs to the maintenance of Tfh cell function and identity. Induced ablation of Cxcr5 in CD4+ T cells had only minor effects on the identity and function of established Tfh cells. Phenotypical and transcriptional analyses revealed that Cxcr5-ablated cells still exhibited most features of CXCR5-positive Tfh cells. In contrast, continued Bcl6 expression was essential to maintain the GC Tfh cell phenotype and GC reaction. CD4+ T cell-specific Bcl6 ablation during acute viral infection resulted in transdifferentiation of established Tfh cells into Th1 cells. Finally, induced depletion of all mature miRNAs resulted in the loss of the Tfh cell phenotype and resolution of GCs. By highlighting the high degree of Tfh cell plasticity, these studies provide novel insights into the mechanisms underlying Tfh cell and GC maintenance.
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Professor Dirk Baumjohann, University Hospital Bonn, Germany
Professor Dirk Baumjohann, University Hospital Bonn, Germany
Dirk Baumjohann studied Molecular Medicine at the University of Erlangen-Nuremberg, Germany, and obtained his PhD degree in Cell Biology/Immunology for work at the Institute for Research in Biomedicine, Bellinzona, Switzerland. He performed his postdoctoral training at the University of California, San Francisco, USA, and then moved to LMU Munich, Germany, as an independent German Research Foundation (DFG)-funded Emmy Noether Research Group Leader. Since 2020, he is Professor of Autoimmunity at University Hospital Bonn, Germany. He has a long-standing interest in dissecting the requirements for T helper cell differentiation and function in various physiological and disease settings, including infection, vaccination, and autoimmunity, with a particular focus on T follicular helper cells and T cell-B cell interactions in germinal centers.
15:40-16:05
Talk 8: Maintenance of GC Tfh Response in Humans
Professor Hideki Ueno, Graduate School of Medicine, Kyoto University, Japan
Abstract
Immunological memory is fundamental to protect the host from a re-infection of the pathogen. The maintenance of humoral memory is mediated by long-lived plasma cells and memory B cells. Their development requires helper signals, including CD40, provided by T follicular helper (Tfh) cells in germinal centers (GCs). GC-Tfh cells participate in the selection of high-affinity B cells and their differentiation into long-lived plasma cells and memory B cells and therefore are fundamental for the generation of durable humoral responses.
Memory Tfh cells play essential roles in the secondary Ab response and provide help to memory B cells and naïve B cells. Memory Tfh cells are present in blood circulation as well as lymphoid organs. The molecular mechanism required for the development of memory Tfh cells remains poorly defined. In my seminar, I will provide evidence that transcription factor Tox2 is important for the maintenance of GC Tfh cells both in humans and mice. I will also share our recent analysis on single cell RNAseq data of human tonsillar CD4+ T cells regarding the plasticity of human GC Tfh cells.
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Professor Hideki Ueno, Graduate School of Medicine, Kyoto University, Japan
Professor Hideki Ueno, Graduate School of Medicine, Kyoto University, Japan
Dr Ueno graduated from Kyoto University, Faculty of Medicine in 1992, and obtained a PhD in Post-Graduate School of Medicine, Kyoto University in 2000. He moved to Baylor Institute for Immunology Research in Dallas, Texas, in 2001 as a post-doctoral fellow and became a faculty as an Assistant Investigator in 2004. He was in charge of monitoring the immune responses in melanoma patients undergoing DC-based vaccine as the Director of the Immunomonitoring Core since 2004. He was promoted to Full Investigator in 2011. He moved to Icahn School of Medicine at Mount Sinai, New York, in 2016, as a Professor in the Department of Microbiology. He also obtained the Professor position at the Department of Immunology in Post-Graduate School of Medicine, Kyoto University last year. He is currently under a cross-appointment agreement between Mount Sinai and Kyoto University.
16:05-16:30
Additional Q&A for talks 6-8 and discussion
16:30-16:35
Closing remarks