Rebuilding the human thymus to create a tolerising system
Research type
Research Study
Full title
Rebuilding the human thymus to create a tolerising system for allogeneic tissue and organ transplantation
IRAS ID
183654
Contact name
Paola Bonfanti
Contact email
Sponsor organisation
UCL Institute of Child Health
Duration of Study in the UK
4 years, 11 months, 30 days
Research summary
Large multicellular organisms, such as humans, need to distinguish their own cells - "self" - from "non-self", so that they can mount a suitable response. Our bodies need to recognise an invading bacteria, virus, or cancerous cell and activate our immune system so that it can respond to protect us from potentially harmful agents. This is called immunity. At the same time, we need a system to recognise our own healthy cells in order not to attack and destroy them - this is called tolerance.
The thymus evolved as a sophisticated machinery to control the balance between immunity and tolerance, by instructing specialised cells called T cells. The thymus is very important in foetuses and neonates, and when the organ is missing at birth, the children suffer of recurrent and serious infections.
Organ transplantation has revolutionized medicine in recent decades, and it is now possible to transplant many different organs such as kidney, heart, liver and lungs from genetically unrelated individuals to allow survival, often with a good quality of life, of patients with no other treatment options. However, a major problem is that the immune system of the recipient would recognise the transplanted organ as "non-self", and would raise an immune response against the donor organ leading to its rejection. Rejection can currently only be prevented by using drugs that suppress the host's entire immune system, which can lead to a number of long term negative consequences such as chronic infections and even tumours.
The aim of this research is therefore to build, step-by-step, a functional human thymus ex vivo that can be used to properly instruct immune cells with tolerogenic potential. In the future, re-establishing tolerance of a hosts' own cells would be an extremely useful way to manage, and produce lasting benefits, in organ transplantation and stem cell therapy.REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
15/YH/0334
Date of REC Opinion
10 Jul 2015
REC opinion
Favourable Opinion