Function of novel human T cell subsets in host defence (360G-Wellcome-109965_Z_15_Z)
Host defence in tissues requires specialised control of immunity. This is particularly true in the liver and gut, where a balance must be struck between robust defence against pathogens vs immunopathogenic responses against commensal organisms. Recently, novel T-cell subsets with distinct functionality have been identified which are abundant in humans at these sites and which may play a central role in tissue defence and inflammation. These include T-cell subsets expressing the C-Type lectin CD1 61 - CD161++ (or bright) Mucosal Associated Invariant T (MAIT) cells and related CD161+ (or mid) antiviral T-cell populations. Although we have learned much about the basic features of these cells in blood, we still do not understand how they are regulated in tissue and there remain many fundamental questions as to their protective and pathogenic roles. In particular we have uncovered common mechanisms that allow innate stimuli to induce triggering, alone or in concert with the T-cell receptor. The vision of my proposal is, therefore, that by identifying the mechanisms that regulate function of such human T-cell subsets, we can delineate and modulate host defence in the liver and gut. There are 3 research questions: 1. What are the protective and pathogenic functions of CD161++/MAIT cells in the human liver and gut and how are these regulated? 2. What are the origins and functions of related CD161+ T-cell memory pools in these tissues? 3. How are CD8+ T-cells induced by novel vac cines maintained in such tissues long-term?
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Grant Details
Amount Awarded | 1650000 |
Applicant Surname | Klenerman |
Approval Committee | Science Interview Panel |
Award Date | 2015-12-02T00:00:00+00:00 |
Financial Year | 2015/16 |
Grant Programme: Title | Investigator Award in Science |
Internal ID | 109965/Z/15/Z |
Lead Applicant | Prof Paul Klenerman |
Partnership Value | 1650000 |
Planned Dates: End Date | 2022-01-31T00:00:00+00:00 |
Planned Dates: Start Date | 2016-08-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | South East |