Regulatory T cells

Summary

Regulatory T cells (Tregs) control autoimmune, allergic and inflammatory responses, and are involved in organ transplantation and immune responses to cancer.

Supervisor(s)

Professor Barbara Fazekas

Research Location

Camperdown - Centenary Institute

Program Type

Masters/PHD

Synopsis

Regulatory T cells comprise a small subset of CD4 T cells that are essential for the control of immune responses. Severe deficiencies in Treg cells lead to fatal diseases in which allergy and autoimmunity are rampant. Such rare diseases are seen both in murine models and in human populations. More subtle deficits in regulatory T cells are believed to increase susceptibility to the common autoimmune, allergic and inflammatory conditions. The prevalence of these conditions is increasing in Western countries, and has been attributed to “clean” living conditions. However, whether such conditions affect the number or function of regulatory cells remains unclear. Our studies are aimed at defining the way in which regulatory T cells function in vivo, how their number and function is controlled under normal circumstances, and whether they are directly or indirectly affected by “clean” living conditions. We are using a combination of different techniques to address these questions: mouse models in which regulatory T cell development and/or function is compromised, studies of Treg cells from healthy volunteers, and studies of Treg cells in patients with autoimmune, allergic and inflammatory diseases. Inflammatory bowel disease (IBD occurs spontaneously in mice deficient in Treg cells. Our main clinical focus is also on IBD, so that we can draw parallels between mouse and man. We have recently defined what appears to be a primary deficit in Treg cells in patients with inflammatory bowel disease. We will test the genetic versus environmental contributions to Treg number using twin studies, in addition to studying the involvement of Treg cells in the pathophysiology of IBD in gut mucosa, lymph nodes and blood. Treg cells are also believed to mediate graft tolerance and to suppress immune responses to cancer, two areas in which we will be initiating projects in the near future.

Additional Information

Techniques:

  • Flow cytometry - the Centenary Institute has a world-class flow cytomety facility with over $3M of sorting and analysis equipment. We routinely perform 8-9 colour sorting and analysis.
  • Intravital microscopy - the Centenary Institute is purchasing a state-of-the-art 2-photon intravital microscope in mid 2007
  • Confocal microscopy - the Centenary Institute is purchasing a state-of-the-art confocal microscope in mid 2007
  • Transgenic and knockout mice - the Centenary Institute has an outstanding track record of making and using genetically manipulated mouse strains. The on-site animal facility is an Australian leader in mouse husbandry and complex breeding.
Research topics for PhDs: Regulatory T cells in human inflammatory bowel disease (IBD) (comprising Crohn’s disease and ulcerative colitis)
  • Correlate the number and phenoype of Treg cells in mucosa, lymph nodes and blood from IBD patients
  • Test whether deficits in regulatory T cells are also present in relatives of IBD patients, and test concordance between mono-and dizygotic twins
  • Test function of IBD regulatory T cells in vitro
Novel mechanisms of regulatory T cell function in mouse and man
  • From transcriptional profiling of regulatory T cells before and after activation in vivo, we have a number of promising candidates that appear to be involved in function
  • These candidates will be tested using a variety of techniques including antibody blocking and gene knockout, where appropriate
  • We will also test mediators known to be involved in control of dendritic cell function (see below)
Regulatory T cell control of dendritic cell function in mouse and man
  • We have evidence that regulatory T cells control the expression of costimulatory molecules by dendritic cells
  • This project aims to determine how regulatory T cells achieve such control and how it affects the behaviour of T cells throughout the immune response.
  • The project will make use of novel transgenic models in which large numbers of antigen-specific regulatory T cells are generated

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Keywords

Inflammatory bowel disease, Crohn's disease, Ulcerative colitis, Asthma, Organ transplantation, Cellular immunology, T cell, Regulatory T cell, tolerance, autoimmune disease, allergy, transplantation, Cancer immunology, Mucosal immunology, Infectious diseases, Cell biology, Infection & immunity

Opportunity ID

The opportunity ID for this research opportunity is: 217

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