Turnover, differentiation and senescence of CD8 memory T cells in vivo (360G-Wellcome-093053_B_10_Z)

£53,397

This proposal employs high-resolution modifications of several elegant techniques to examine whether CD57+ memory T-cells are truly senescent. The techniques employed include in vivo stable isotope labelling of human subjects with deuterated water, state-of-the-art multiparameter flow cytometric sorting, and T-cell clonotyping. Recent refinements to these techniques now allow reliable measurements from very low numbers of cells. Therefore, it is now possible to take full advantage of the power o f multiparameter, multidirectional fluorescence-activated cell sorting to simultaneously measure the kinetics of multiple, even rare, subpopulations of cells, including memory CD57+ CD8+ T-cells that are infrequent in healthy subjects. The key goal of this proposal is to reveal whether CD57+ CD8+ T-cells as well as antigen-specific CD57+ CD8+ T-cells accumulate in chronic infections because of increased proliferation or because of phenotypic conversion from a precursor memory T-cell subset. This information will help to illuminate the ontogeny and significance of memory CD57+ CD8+ T-cells and determine the impact of specific antigen-driven processes in the generation and maintenance of this enigmatic memory T-cell subset.

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Grant Details

Amount Awarded 53397
Applicant Surname Macallan
Approval Committee Immunology and Infectious Disease Funding Committee
Award Date 2010-10-05T00:00:00+00:00
Financial Year 2010/11
Grant Programme: Title Project Grant
Internal ID 093053/B/10/Z
Lead Applicant Dr Derek Macallan
Other Applicant(s) Prof David Price
Partnership Value 53397
Planned Dates: End Date 2016-12-31T00:00:00+00:00
Planned Dates: Start Date 2012-01-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London