Thymus transplantation for the treatment of Complete DiGeorge syndrome. (360G-Wellcome-094255_Z_10_Z)
Without intervention, complete DiGeorge syndrome (DGS) results in fatal immunodeficiency, as a result of absent thymic stromal function. Recent therapies focus on transplantation of non-MHC-matched thymic epithelium. This project will investigate the importance of MHC-restriction in immune reconstitution and self-tolerance in DGS patients treated with transplantation of thymic epithelium. To test if appropriate MHC expression in thymic epithelial transplants is necessary for efficient T-cel l immunity and tolerance-induction, we will compare the ability of T-cells from DGS transplant patients to activate and proliferate in response to MHC (+antigen) of host- or donor-origin. We will also establish in vitro and mouse in vivo models to address this question. We will compare tolerance induction in human thymus reaggregate cultures in which the epithelial and haematopoietic components are either MHC-matched or mismatched. To assess the impact of MHC-matching on immune reconstitution i n vivo, we will generate models in which athymic mice reconstituted with human haematopoietic stem cells, are transplanted with human thymic epithelium, expressing either MHC matched or non-matched to the haematopoietic component. In addition, to test if a gene-therapy approach to MHC-matching would be beneficial, we will test if we can improve reconstitution by lentiviral-transduction of matched MHC into thymic epithelial cells.
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Grant Details
Amount Awarded | 408095 |
Applicant Surname | Crompton |
Approval Committee | Immunology and Infectious Disease Funding Committee |
Award Date | 2011-03-07T00:00:00+00:00 |
Financial Year | 2010/11 |
Grant Programme: Title | Project Grant |
Internal ID | 094255/Z/10/Z |
Lead Applicant | Prof Tessa Crompton |
Other Applicant(s) | Dr Anna Furmanski, Dr Graham Davies, Prof Adrian Thrasher |
Partnership Value | 408095 |
Planned Dates: End Date | 2017-03-29T00:00:00+00:00 |
Planned Dates: Start Date | 2012-12-30T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |