Research

Overview

  • Cellular immunology
  • Autoimmune disease
  • Type 1 diabetes
  • Cytokines
  • T regulatory cells
  • CD8+ T cells

The Green Lab is interested in the mechanisms by which the immune system regulates autoaggressive cells that target and destroy host tissue. The autoimmune disease, Type 1 Diabetes in which the insulin producing beta cells in the islets of Langerhans are destroyed, is a particular focus. Using a series of transgenic and gene knockout models, we are deciphering the role of individual immune cells in the diabetic process in the hope of developing novel therapies to eradicate the disease.

In addition, we are interested in identifying the key signal pathways that enable development of Foxp3+ regulatory T cells in the thymus and periphery as well as the mechanisms that control their survival and functionality in inflamed tissue.

Projects

Cytokines in the development, or control, of type 1 diabetes

It has long been established that cytokines produced by immune cells contribute to the inflammatory environment and enable destruction of beta cells either directly through their toxic properties, or indirectly by potentiating the activity of other cells. Two cytokines we are particularly interested in are Tumour Necrosis Factor Alpha (TNFα) and Transforming Growth Factor Beta (TGFβ). TNFα is a pro-inflammatory cytokine linked to type 1 diabetes progression in both man and mouse whereas TGFβ is a major immunosuppressive cytokine that can switch autoaggressive immune cells off. Using a series of unique models, where we can control expression of these cytokines in the islets, we are deciphering the immune mechanisms by which TNFα can potentiate an autoaggressive response and TGFβ can disable it. In addition, in collaboration with Dr. Maja Wallberg at Cambridge University, we are exploring the potential of using TGFβ-expressing islets as donor cells in the transplantation setting.

Deciphering the B cell: CD8+ T cell axis in Type 1 Diabetes

Although B cells had been known to have a critical role to play in the development of diabetes in murine models of Type 1 Diabetes, their importance in man was debateable. However, recent clinical trials using the B cell-depleting antibody rituximab documented the ability of the antibody to reverse diabetes in newly diagnosed patients. In terms of CD8+ T cells, recent research in humans has led to an increasing body of evidence that CD8+ T cells are central to beta cell destruction. The mechanisms by which B cells and CD8+ T cells can lead to diabetes development are not clear. We have new evidence that B cells and CD8+ T cells collaborate together to enable the CD8+ T cells to evolve into cytotoxic killers of beta cells. Currently, we are investigating the immune mechanisms behind this collaborative event.

Costimulatory signals in the development of Foxp3+ regulatory T cell development.

Over the past decade the importance of a unique lineage of T cells, called Foxp3+ regulatory (Treg) T cells, has dominated the research community. Linked to the control of autoimmune disease, dampening of the immune response after clearance of viral/bacterial infections, and adversely promoting cancer development, the potential to manipulate Treg cells to benefit man has been a hot topic. One area of Treg biology we are interested in is the role of costimulatory molecules that are required for Foxp3+ Treg development and/or survival and functionality in inflamed tissue. One such co-stimulatory pathway that we have shown to be important in Treg cell development is the CD40-CD154 immune regulatory pathway, the abrogation of which results in a dramatic impairment in Treg cell generation. Using a series of gene knockout models, we are deciphering the reason why CD40-CD154 signals are important in triggering Treg development from bone marrow derived progenitor cells. It is hoped that such investigations will provide new insights into how manipulation of the pathways CD40-CD154 signals control could be used therapeutically to control Treg cell numbers positively or negatively depending on the immune setting.

Research group(s)

NameStatusProject
    Thymic B cells as mediators of Type 1 Diabetes

 

Grants

  • The Wolfson Foundation Fellowship
    Intrathymic B cells as mediators of autoimmune type 1 diabetes
  • Hull York Medical School
    Identification of unique genetic signatures of thymic resident and developing Treg cells in health and disease 
  • The Wellcome Trust
    Inflammation and the control, or perpetuation, of autoimmunity
  • The Wellcome Trust
    Wellcome Trust 4yr PhD studentship in Infection and Immunity Program  (Cambridge University):The CD40-CD154 pathway in Foxp3+ regulatory T cell biology

Allison Green
Senior Lecturer in Immunology

Profile

Biography

Allison Green is a Senior Lecturer in Immunology. Previously she was Wellcome Senior Research Fellow in Basic Biomedical Science in the Centre for Immunology and Infection (CII) and HYMS and joined the Centre in 2010. She obtained her BSc in Immunology from Glasgow University (UK), a PhD in Virology, Immunology and Vaccination at St. Andrews University (UK) and then moved to Yale School of Medicine (USA) to conduct postdoctoral research in the laboratory of Richard Flavell. Whilst here, she obtained a Juvenile Diabetes Research (JDRF) Postdoctoral Fellowship, followed by a JDRF Career Development Award. In 2001, she was recruited to Cambridge University (UK) to set up her own laboratory funded by a Wellcome Trust/JDRF Career Development Award and subsequently a Wellcome Senior Research Fellowship in Basic Biomedical Science. In 2002, she was the first recipient of the GJ Thorbecke Award from the International Society for Leukocyte Biology in recognition of her work in inflammation and disease.

Career

  • St Andrew's University
    PhD in Virology
  • Yale School of Medicine
    Postdoctoral Researcher
    Juvenile Diabetes Research Postdoctoral Fellowship
    Juvenile Diabetes Research Fellowship Career Development Award
  • Cambridge University
    Wellcome Trust/JDRF Career Development Fellow
    Wellcome Trust Senior Research Fellow
  • University of York
    Wellcome Trust Senior Research Fellowship ( - Feb 2011)
    Senior Lecturer in Immunology (Feb 2011 - )

Publications

Selected publications


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Contact details

Dr Allison Green
Senior Lecturer in Immunology, HYMS
Centre for Immunology and Infection
University of York
Heslington
York
YO10 5DD

Tel: 01904 328916
Fax: 01904 328844