Analysing the phenotype and function of regulatory T cells

Tuesday, 04 April 2006

Analysing the phenotype and function of regulatory T cells
Tuesday, 04 April 2006 09:15 - 16:30

Birkbeck College
Room B04
Malet Street
United Kingdom

Map and Directions

Suppressor T cells, after several decades in the dark, are now very much back in focus as key immunoregulatory T cells. Despite extensive interest and research in this area, many of the precise characterisics of these naturally anergic and suppressive cells are unclear, namely their specific markers, the importance of cytokines and costimulatory molecules in their action, the ligands on APC and their propagation in an antigen specific manner.  Similarly, the importance of  their role in early embryonic development, allergy, autoimmunity and transplantation is becoming increasingly clear.  This meeting will illuminate the latest findings in many of these areas, and will provide an ideal forum for discussion with scientists currently working on regulatory T cells and those seeking to set up research in this area.” - Dr Catherine Derry - Meeting's Chair


9.00 - 9:30      Registration - tea/coffee and biscuits

9:30 - 9:35      
Introduction by the Chair - Dr Catherine Derry

9:35 - 10:00    Identifying regulatory T cells at the fetal-maternal interface:  Functions and therapeutic potential of Tregs for pregnancy complications
Dr Ana Claudia Zenclussen - Institute of Medical Immunology, Charité, Germany

Tolerance mechanisms are responsible for the survival of the fetus within the maternal uterus without being attacked by cells of the maternal immune system despite their direct contact. Regulatory T cells (Treg) were claimed to be important players in tolerance towards the fetus bearing alloantigens. Recent evidences confirmed an augmentation in the number of Treg during pregnancy and diminished number of Treg was associated with immunological rejection of the fetus. This could be prevented by adoptively transferring CD4+CD25+ cells from normal pregnant mice into abortion-prone animals. Treg prevented abortion by creating a transient tolerant microenvironment characterized by high levels of TGF-beta, LIF and HO-1. Further, we have evidences suggesting that Treg need to be activated by male antigens during pregnancy for being protective.

10:00 - 10:25  
Tracking antigen specific regulatory T cells in autoimmune disease
Dr Lucy Walker, University of Birmingham
TCR transgenic model to study antigen-specific Tregs.  Tracking migration and activation during onset and progression of autoimmune diabetes.

10:25 - 10:50  Induction of antigen-specific regulatory T cells for treatment of allergy and autoimmune

Professor David C Wraith- University of Bristol

Immunoregulatory cells limit the pathological consequences of the immune response to self and foreign antigens.  ‘Natural’ CD25hi immunoregulatory cells have been studied extensively and shown to express Foxp3.  A distinct population of regulatory cells can be induced, however, by injection of soluble peptides.  Peptide treatment elicits regulatory T cells that are anergic and IL-10 dependent.  IL-10+ Treg can be generated in an environment lacking CD25hi regulatory cells proving that ‘natural’ and ‘induced’ regulatory cells fall into distinct subsets.  Peptide induced Treg cells do not express FoxP3, the forkhead-winged helix family transcription factor that controls differentiation of ‘natural’ CD25+ Treg cells.

10:50 - 11:15  Enhanced suppressive capacities of regulatory T cells under therapy with interferon-beta and glatiramer acetate in patients with Multiple Sclerosis

Dr.  Juergen Haas, University of Heidelberg, Germany

Treg appear to play a crucial role in the pathogenesis of autoimmune diseases such as multiple sclerosis, although their mechanism of action is not yet understood. Recent studies have shown diverse effects of drugs on Treg, either influencing their content of FoxP3 mRNA, surface-marker pattern or their longevity. However, there is little data concerning the influence of drugs on their inhibitory capacity. Data elucidating the changes that suppressive capacity of Treg might undergo in peripheral blood of patients receiving long term treatment with immunomodulatory drugs are equally scarce, as these drugs act upon both diverse lymphocyte subsets and antigen presenting cells

11:15 - 11:45  Mid-morning break: tea/coffee

11:45  - 12:10  
Regulatory T cells in Rheumatoid Arthritis
Dr Michael Ehrenstein, UCL 
Anti-TNF therapy regulates CD4+CD25high T cells levels and function in Rheumatoid Arthritis. We have demonstrated that regulatory T cells isolated from patients with active RA, although still anergic, they were unable to suppress pro-inflammatory cytokines released by T cells and monocytes. In addition, these regulatory T cells lack the ability to convey a suppressive phenotype to neighbourhood effectors T cells. The functional defect was not permanent, as suppressive activity was restored after anti-TNF treatment. Furthermore, anti-TNF treatment lead to a significant rise in the peripheral blood regulatory T cells of RA patients responding to this treatment, which correlated with a reduction in C reactive Protein (CRP).

12:10 - 12:35  Modulation of the immune response in rheumatoid arthritis by regulatory T cells

Dr Leonie Taams – Kings College, London
CD4+CD25+ regulatory T-cells (Tregs) are effective suppressors of T-cell responses. Upon interaction of monocytes with Tregs also profound changes in monocyte/macrophage phenotype and function are observed. For example, the antigen- and allospecific T-cell-stimulatory capacity of Treg-treated monocytes is decreased whilst their phagocytic capacity is slightly enhanced. Furthermore, Tregs have an immediate suppressive effect on IL-6 production by monocytes, a cytokine known to make T-cells resistant to Treg-mediated suppression. Our data indicate that IL-10 plays a key role in the suppressive effects, and that Treg-monocyte contact is required for this IL-10 production. We are currently investigating additional mechanisms and consequences of Treg-mediated suppression of monocytes.

12:35  - 13:00  Roles of IL-10 and CTLA-4 in control of intestinal inflammation by CD4+ CD25+TR
Dr. Ana Izcue, Oxford University
Transfer of CD45Rbhi naive T cells into immunodeficient mice induces a series of disorders that include wasting disease and colitis. These effects can be prevented by the cotranfer of CD4+ CD25+ TR, which act through several mechanisms including CTLA-4 and IL-10. These two molecules are employed at different levels for regulation. Whereas CTLA-4 seems to have systemic effects, IL-10 appears to be specifically required to prevent and cure intestinal pathology. This talk will discuss how CD4+ CD25+ TR deal with inflammation in systemic and local compartments, focusing on intestinal

13:00 - 14:00  Lunch in the exhibition hall

14:00– 14:25 Therapeutic applications of antigen-specific regulatory T cells for transplantation
Dr Jian-Guo Chai, Imperial College of Science, Technology & Medicine, London.

Naturally occurring CD4+CD25+ regulatory T cells are critical for maintaining T cell tolerance to self and non-self antigens and have tremendous clinical potential. Clinical application is however frustrated by their scarcity, anergic status and lack of defined specificity. To overcome these hurdles,  three distinct in vitro approaches have been established in our group to generate a large number of HY-specific regulatory T cells that are capable of inducing transplantation tolerance in vivo.

14:25 - 14:50  The influence of CD4 T cell subsets on control of graft versus host disease
Dr Halima Moncrieffe - The National Institute of Medical Research
To study the effect of different T cell subpopulations on antigen driven expansion, we used a model of graft versus host disease. We find less disease incidence and severity with cotransfer of CD4+CD25+ T cells or memory CD4+ T cells. Cell recovery and stereomicroscopy data demonstrate a difference in the location of these two regulatory populations post-transfer. CD4+CD25+ cells inhibit IFNg production of the naïve input and are primarily found in the lymphoid organs post-transfer whereas memory cells are found systemically.

14:50 - 15:15  Purification of T regulatory cells from whole blood: Applications to the studies of T
regulatory  cell modifying drugs

Mr Brendan Meyer - St Georges Medical School, University of London
T regulatory cells represent a small percentage of the population of  peripheral blood cells and are important modulators of T cell immunity. The talk will discuss the challenges involved in the isolation of T regulatory cells, the methods used, and the use of the purified cells to investigate mechanisms of action of a group of drugs known as the IMiDs. These drugs are analogs of the drug thalidomide, and have co-stimulatory activities on T cells. We show that these drugs have actions against T regulatory cells, and that this is a possible mechanism for their effects in-vivo.

15:15- 15:45  Afternoon tea/coffee and cakes in the exhibition hall

15:45 – 16:10 Isolation and analysis of CD4+CD25+ regulatory T cells
Doris Hasselmann, Miltenyi Biotec, Germany

16:10 – 16:35  CD4+ CD25high Regulatory T Cells, From Isolation to Expansion
Dr Thomas Bauer, Invitrogen Corporation

16:35 - 17:00  Quantifying Human CD4+CD25High Regulatory T-Cells: A Challenge
Dr Frederique Ponchel Leeds Institute for Molecular Medicine, St. James’s University HospitalThe functional properties of CD4+CD25+ regulatory T-cells (Treg) are now well established, however, their quantification in a number of human diseases remains a point of debate. Discrepant frequencies have been reported for CD4+CD25+ or CD4+CD25high Treg in health, as well as in diseases, including diabetes, multiple sclerosis, cancer, rheumatoid arthritis and leishmaniasis. There are a number of reasons for these differences, which are compounded by the difficulties in defining a quantification strategy. Several antibodies for CD25 are commercially available, but they differ in their sensitivity. Variability between individuals is likely to contribute to the discrepancies. Finally, flow-cytometers and gating strategies may also add to the differences reported between studies. We undertook an analysis of these different parameters to assess which of them is the most likely contributor to the discrepancies reported in the literature. We used 5 commercially available CD25 antibodies (used in published work), comparing 10 healthy individuals using 3 different flow-cytometers and used a Kolmogorov-Smirnov- statistical analysis gating on each participant‘s CD4- CD25+ cells. Our data showed that all 3 factors (antibody, population variability and gating strategy) contribute to the published differences and we are currently analysing disease patients to further our findings.

17:00            Chairman's summing up

Registraton fees

  • Standard fee - £360
  • Academic fee - £180
  • Student fee- £140
  • IBMS members fee - £199



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