6 results on '"Hanna, Stephanie J"'
Search Results
2. Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans.
- Author
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Hanna, Stephanie J., Thayer, Terri C., Robinson, Emma J. S., Vinh, Ngoc-Nga, Williams, Nigel, Landry, Laurie G., Andrews, Robert, Qi Zhuang Siah, Leete, Pia, Wyatt, Rebecca, McAteer, Martina A., Nakayama, Maki, Wong, F. Susan, Yang, Jennie H. M., Tree, Timothy I. M., Ludvigsson, Johnny, Dayan, Colin M., and Tatovic, Danijela
- Subjects
INTRADERMAL injections ,GOLD nanoparticles ,T cells ,TYPE 1 diabetes ,PEPTIDES - Abstract
Gold nanoparticles (GNPs) have been used in the development of novel therapies as a way of delivery of both stimulatory and tolerogenic peptide cargoes. Here we report that intradermal injection of GNPs loaded with the proinsulin peptide C19-A3, in patients with type 1 diabetes, results in recruitment and retention of immune cells in the skin. These include large numbers of clonally expanded Tcells sharing the same paired T-cell receptors (TCRs) with activated phenotypes, half of which, when the TCRs were re-expressed in a cell-based system, were confirmed to be specific for either GNP or proinsulin. All the identified goldspecific clones were CD8+, whilst proinsulin-specific clones were both CD8+ and CD4+. Proinsulin-specific CD8+ clones had a distinctive cytotoxic phenotype with overexpression of granulysin (GNLY) and KIR receptors. Clonally expanded antigen-specific T cells remained in situ for months to years, with a spectrum of tissue resident memory and effector memory phenotypes. As the T-cell response is divided between targeting the gold core and the antigenic cargo, this offers a route to improving resident memory T-cells formation in response to vaccines. In addition, our scRNAseq data indicate that focusing on clonally expanded skin infiltrating T-cells recruited to intradermally injected antigen is a highly efficient method to enrich and identify antigen-specific cells. This approach has the potential to be used to monitor the intradermal delivery of antigens and nanoparticles for immune modulation in humans. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
3. T cell phenotypes in COVID-19 - a living review
- Author
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Hanna, Stephanie J, Codd, Amy S, Gea-Mallorqui, Ester, Scourfield, D Oliver, Richter, Felix C, Ladell, Kristin, Borsa, Mariana, Compeer, Ewoud B, Moon, Owen R, Galloway, Sarah A E, Dimonte, Sandra, Capitani, Lorenzo, Shepherd, Freya R, Wilson, Joseph D, Uhl, Lion F K, Ahern, David J, Almuttaqi, Hannah, Alonzi, Dominic S, Alrubayyi, Aljawharah, Alsaleh, Ghada, Bart, Valentina M T, Batchelor, Vicky, Bayliss, Rebecca, Berthold, Dorothée L, Bezbradica, Jelena S, Bharuchq, Tehmina, Borrmann, Helene, Borst, Rowie, Brun, Juliane, Burnell, Stephanie, Cavounidis, Athena, Chapman, Lucy, Chauveau, Anne, Cifuentes, Liliana, Codd, Amy Susan, Compeer, Ewoud Bernardus, Coveney, Clarissa, Cross, Amy, Danielli, Sara, Davies, Luke C, Dendrou, Calliope A, Peter Durairaj, Ruban Rex, Dustin, Lynn B, Dyer, Arthur, Fielding, Ceri, Fischer, Fabian, Gallimore, Awen, Galloway, Sarah, Gammage, Anís, Gea-Mallorquí, Ester, Godkin, Andrew, Heuberger, Cornelia, Hulin-Curtis, Sarah, Issa, Fadi, Jones, Emma, Jones, Ruth, Lauder, Sarah N, Liddiard, Kate, Ligoxygakis, Petros, Lu, Fangfang, MacLachlan, Bruce, Maleki-Toyserkani, Shayda, Mann, Elizabeth H, Marzeda, Anna M, Matthews, Reginald James, Mazet, Julie M, Milicic, Anita, Mitchell, Emma, Moon, Owen, Nguyen, Van Dien, OHanlon, Miriam, Eléonore Pavillet, Clara, Peppa, Dimitra, Pires, Ana, Pring, Eleanor, Quastel, Max, Reed, Sophie, Rehwinkel, Jan, Richmond, Niamh, Richter, Felix Clemens, Robinson, Alice J B, Rodrigues, Patrícia R S, Sabberwal, Pragati, Sami, Arvind, Peres, Raphael Sanches, Sattentau, Quentin, Schonfeldova, Barbora, Scourfield, David Oliver, Selvakumar, Tharini A, Shorten, Cariad, Simon, Anna Katharina, Smith, Adrian L, Crespo, Alicia Teijeira, Tellier, Michael, Thornton, Emily, van Grinsven, Erinke, Wann, Angus K T, Williams, Richard, Zhou, Dingxi, Zhu, Zihan, Gallimore, Awen M, and Consortium, Oxford-Cardiff COVID-19 Literature
- Subjects
0301 basic medicine ,T cell ,Short Communication ,T cells ,Biology ,phenotypes ,COVID-19 ,antigen-specific ,peripheral blood ,lung ,Virus ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Lung ,Mechanism (biology) ,General Medicine ,Acquired immune system ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunology ,AcademicSubjects/SCI00960 ,Function (biology) - Abstract
COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients’ long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation.
- Published
- 2020
4. Differentiating MHC-Dependent and -Independent Mechanisms of Lymph Node Stromal Cell Regulation of Proinsulin-Specific CD8+ T Cells in Type 1 Diabetes.
- Author
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Thayer, Terri C., Davies, Joanne, Pearson, James A., Hanna, Stephanie J., Wen, Li, and Wong, F. Susan
- Subjects
TYPE 1 diabetes ,T cells ,CELLULAR control mechanisms ,STROMAL cells ,LYMPH nodes ,DENDRITIC cells ,RESEARCH ,ANIMAL experimentation ,RESEARCH methodology ,MEDICAL cooperation ,EVALUATION research ,COMPARATIVE studies ,PROINSULIN ,CONNECTIVE tissue cells ,HISTOCOMPATIBILITY antigens ,MICE - Abstract
Lymph node stromal cells (LNSC) are essential for providing and maintaining peripheral self-tolerance of potentially autoreactive cells. In type 1 diabetes, proinsulin-specific CD8+ T cells, escaping central and peripheral tolerance, contribute to β-cell destruction. Using G9Cα-/-CD8+ T cells specific for proinsulin, we studied the mechanisms by which LNSC regulate low-avidity autoreactive cells in the NOD mouse model of type 1 diabetes. Whereas MHC-matched NOD-LNSC significantly reduced G9Cα-/-CD8+ T-cell cytotoxicity and dendritic cell-induced proliferation, they failed to sufficiently regulate T cells stimulated by anti-CD3/CD28. In contrast, non-MHC-matched, control C57BL/6 mouse LNSC suppressed T-cell receptor engagement by anti-CD3/CD28 via MHC-independent mechanisms. This C57BL/6-LNSC suppression was maintained even after removal of the LNSC, demonstrating a direct effect of LNSC on T cells, modifying antigen sensitivity and effector function. Thus, our results suggest that a loss of NOD-LNSC MHC-independent suppressive mechanisms may contribute to diabetes development. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
5. T cell phenotypes in COVID-19 - a living review.
- Author
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Hanna, Stephanie J, Codd, Amy S, Gea-Mallorqui, Ester, Scourfield, D Oliver, Richter, Felix C, Ladell, Kristin, Borsa, Mariana, Compeer, Ewoud B, Moon, Owen R, Galloway, Sarah A E, Dimonte, Sandra, Capitani, Lorenzo, Shepherd, Freya R, Wilson, Joseph D, Uhl, Lion F K, The Oxford-Cardiff COVID-19 Literature Consortium, Ahern, David J, Almuttaqi, Hannah, Alonzi, Dominic S, and Alrubayyi, Aljawharah
- Subjects
T cells ,PSYCHONEUROIMMUNOLOGY ,IMMUNOLOGIC memory ,COVID-19 ,PHENOTYPES ,VACCINE development - Abstract
COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients' long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
6. Peripheral Proinsulin Expression Controls Low-Avidity Proinsulin-Reactive CD8 T Cells in Type 1 Diabetes.
- Author
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Thayer, Terri C., Pearson, James A., De Leenheer, Evy, Hanna, Stephanie J., Boldison, Joanne, Davies, Joanne, Tsui, Adrian, Ahmed, Sartaj, Easton, Peter, Lai Khai Siew, Li Wen, Wong, F. Susan, Siew, Lai Khai, and Wen, Li
- Subjects
PROINSULIN ,CYTOTOXIC T cells ,CELL physiology ,T cell receptors ,TYPE 1 diabetes ,TRANSGENIC mice ,ANIMAL experimentation ,ANTIGENS ,FLOW cytometry ,INSULIN ,MICE ,T cells - Abstract
Low-avidity autoreactive CD8 T cells (CTLs) escape from thymic negative selection, and peripheral tolerance mechanisms are essential for their regulation. We report the role of proinsulin (PI) expression on the development and activation of insulin-specific CTLs in the NOD mouse model of type 1 diabetes. We studied insulin B-chain-specific CTL from different T-cell receptor transgenic mice (G9Cα-/-) expressing normal PI1 and PI2 or altered PI expression levels. In the absence of PI2 (Ins2-/-), CTL in pancreatic lymph nodes (PLNs) were more activated, and male G9Cα-/- mice developed T1D. Furthermore, when the insulin-specific CTLs developed in transgenic mice lacking their specific PI epitope, the CTLs demonstrated increased cytotoxicity and proliferation in vitro and in vivo in the PLNs after adoptive transfer into NOD recipients. Dendritic cell-stimulated proliferation of insulin-specific T cells was reduced in the presence of lymph node stromal cells (LNSCs) from NOD mice but not from mice lacking the PI epitope. Our study shows that LNSCs regulate CTL activation and suggests that exposure to PI in the periphery is very important in maintenance of tolerance of autoreactive T cells. This is relevant for human type 1 diabetes and has implications for the use of antigen-specific therapy in tolerance induction. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
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