MRC Centre sweeps the boards in New York

Posted: 10 September 2010

The Centre had a good presence at last month’s XXII International Complement Workshop in New York, presenting no fewer than six talks and winning four prizes.

Congratulations to PhD student John Cardone for winning a travel award for his talk “CD46 favours immunoregulation by promoting the switch of Th1 cells into IL-10 producing Treg cells” and to Research Associate Ke Li, also the winner of a travel award for his talk “Influence of complement C5a on natural killer cell function in tumour elimination”. They each received 0.

And well done to Research Associate, Dr Gaëlle le Friec, who was awarded both a 0 travel award and a 0 Trainee Reagent Award sponsored by the Quidel Corporation for demonstrating ‘an excellent research achievement’. The prizes were in recognition for her talks “CD46: Just a Notch up your common complement regulator” and “The complement regulator CD46 regulates unconventional gamma/delta T cell responses”.

The complement receptor CD46 tips the scales in TH1 self-control

Posted: 8 September 2010

Congratulations to Dr Claudia Kemper and fellow Centre colleagues John Cardone, Dr Gaelle le Friec and Professors Adrian Hayday and Graham Lord and Professor Andy Cope from the Academic Department of Rheumatology et al, on the publication of their article Complement regulator CD46 temporally regulates cytokine production by conventional and unconventional T cells Nature Immunology 11; 862-871 August 2010.

The paper, published in the current issue of Nature Immunology, shows how the suppression of unwanted Th1 immune responses against self-antigen is vital to the limitation of autoimmunity. Dr Kemper, who led the study, said “Th1 response (self) control is thought to be mediated by the timely switch from IFN-γ production to the production of the immunosuppressive cytokine IL-10. However, the signals and pathways driving this switch are poorly understood. Our current study identifies the complement regulator CD46 and the cytokine IL-2 as critical drivers of this process and further suggests an important role for this mechanism in the prevention of autoimmune arthritis.”

The paper was also chosen for the News and Views section of the journal in an article by C M Karsten and J Köhl.

Megan Sykes visit hints at future collaboration

Posted: 29 June 2010

We are delighted to report an outstandingly successful visit to the Centre earlier this month by Professor Megan Sykes from Columbia University, New York. Megan and her colleagues at Massachusetts General have developed the only successful transplant tolerance programme involving combined bone marrow and kidney transplantation. During her visit, she met members of the bone marrow transplant team at King’s College Hospital and the renal transplant team at Guy’s. Megan also chaired a seminar with both teams looking at future collaboration to promote a similar programme in London. The highlight of the visit was Megan’s keynote lecture on “Mixed chimerism – transplant tolerance from laboratory to clinic” which was brilliantly delivered to a packed auditorium.

MRC Clinician Scientist Fellowship awarded to Maria Serena Longhi

Posted: 25 June 2010

Congratulations to Dr Maria Serena Longhi of the Institute of Liver Studies, who has been awarded a four-year MRC Clinician Scientist Fellowship.

Dr Longhi’s project, entitled ‘Autoantigen-specific regulatory T-cells: a new tool for tolerance induction in autoimmune hepatitis’, aims to generate and expand phenotypically and functionally stable autoantigen-specific regulatory T-cells from patients with autoimmune hepatitis (AIH) with the ultimate goal to deploy these cells for achieving disease remission, and possibly cure, by autologous adoptive transfer.

“If successful, these studies would offer proof-of-principle for the feasibility of tolerance induction not only in AIH but also in other autoimmune disorders, collectively representing 5% of human disease”

Juvenile AIH is a severe liver disease whose prevalence in the supraregional referral centre at King’s College Hospital has increased six-fold (from 1.2% to 8%) in the last decade. AIH requires life-long immunosuppression, which in addition to causing growth impairment and predisposing to cancer development, does not always prevent transplant-requiring end-stage liver disease. The involvement of autoreactive B, CD4 and CD8 T-cells in the pathogenesis of AIH liver damage is well documented with the three arms of immune response converging on discrete antigenic regions. This multipronged immune attack is permitted by a numerical and functional defect of CD4posCD25pos regulatory T-cells (T-regs), a cell subset central to immune-tolerance reconstitution and maintenance. Generation and expansion of T-regs with the same liver autoantigen specificity of the effectors will allow restoring immune-tolerance to specific antigenic regions, therefore leading to reduced T-cell effector activity and, ultimately, to disease remission. AIH provides an ideal model for the generation and potential therapeutic use of antigen-specific T-regs, as the autoantigenic targets are known. Generation and expansion of liver-specific T-regs will be attempted using different approaches, including co-culture with semi-mature dendritic cells, HLA-class II tetramers and rapamycin.

Besides its translational component, the project will explore important aspects of T-reg biology, namely their functional commitment and stability over time. To this end Dr Longhi will spend one year in the laboratory of Professors Strom and Robson (Beth Israel Deaconess Medical Center, Harvard Medical School) to investigate, in a murine system, the role of CD39 - an ectonuleotidase expressed by T-regs and pivotal to the hydrolysis of ATP into the inhibitory molecule adenosine, in the functional stability of T-regs. As a first step towards their clinical application, liver-specific T-regs will be generated under GMP conditions and their safety tested in a pre-clinical model.

If successful, these studies would offer proof-of-principle for the feasibility of tolerance induction not only in AIH but also in other autoimmune disorders, collectively representing 5% of human disease

Centre PhD students scoop prizes at DIIID PhD Symposium

Posted: 24 June 2010

Two of our talented PhD students have won prizes worth £200 at the DIIID PhD Symposium on 17th June.

John Cardone won ‘Best Poster’ for his work entitled “C46 promotes immunoregulation by favouring the switch of Th1 cells into IL10 secreting Treg cells”. Ehsan Sharif-Paghaleh won the ‘Front Cover Competition’ for his abstract title “In vivo imaging of T-Regulatory cell mediated transplant tolerance”. The front cover depicted his first mouse whole body SPECT imaging of radiolabelled lymphocytes which was also the first of its kind to be done at KCL.

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