Networks that regulate tolerance and promote long term graft acceptance

Within this theme research will study the promotion of long term graft acceptance in man. At the core of the research is work to isolate natural human Treg cells, manipulate them in the laboratory and then use them to promote tolerance of the new graft in patients receiving solid organ, tissue or cell transplants. This work is being carried out by Professors Robert Lechler and Giovanna Lombardi. Clinical application of this work is developing in kidney transplantation in collaboration with colleagues at King's Health Partners (Mr Geoff Koffman, Dr Rachel Hilton and Dr Dave Game). Collaborators in Haematopoietic Cell Transplantation are also helping to develop first in man therapies using this technology (Professor Ghulam Mufti, Professor Tony Pagliuca, Mr Nizam Mamode and Mr Geoff Koffman).

Work formerly led by Professor Randy Noelle researched the importance of Retinoic Acid in promoting the stability of human Treg cells. Retinoic acid has a number of other potential roles which Professor Noelle's group have investigated, including its effect on T cell homing to local lymph nodes and its function in the inflammatory pathway. In addition a new molecule, VISTA, may downregulate the function of T cells and thus promote immunosuppression. Professor Noelle’s group has now relocated to the University of Dartmouth, USA.

Related to the VISTA programme, Professors Paul Sharpe and Giovanna Lombardi are examining immunosuppressive properties of the molecule PDL-1. Additional research teams (Dr Claudia Kemper) are investigating signalling events downstream of complement regulator CD46. Dr Wilson Wong and others are combining local expertise in complement, receptor signalling and T Cell regulation to see whether these can be harnessed for therapeutic patient benefit when combined with the protein therapy approaches being led by Dr Richard Smith.

Immune Intervention: Dr Wilson Wong
Complement: Dr Claudia Kemper
T cell therapy: Professor Robert Lechler, Professor Giovanna Lombardi
Humanised mice: Professor Frank Nestle
Tooth replacement: Professor Paul Sharpe
Haematopoietic stem cell: Professor Ghulam Mufti
Kidney/Pancreas: Mr Nizam Mamode