Grants and Contracts Details
Description
Natural killer (NK) cells use KIR and CD94/NKG2A receptors to detect infected cells and cancer cells that
have downregulated MHCclass I molecules. Declining NK cell function is associated with infection and poor
health in the elderly, but little is know about NK receptor expression or population dynamics in the elderly.
OUR LONG-RANGE GOAL is to manipulate NK cells to promote healthy aging. Our CURRENT
OBJECTIVE is to study human NK population dynamics and turnover in aging, especially as they relate to
age related shifts in NK receptor expression. Supported by our novel preliminary data, our CENTRAL
HYPOTHESIS is that an age related change in NK receptor expression is caused by a change in NK
development and this in turn alters NK function and turnover A feature of this shifting balance is the
accumulation of NK cells with restricted receptor repertoire. The RATIONALE of the proposed research is
that a better understanding of NK population dynamics and shifting NK receptor expression may allow us
manipulate innate immunity in healthy and unhealthy aging. Our SPECIFIC AIM is to investigate human NK
population dynamics as they relate to KIR and CD94/NKG2 receptor expression and other defined NK
subsets. We will 1. test the replication potential and expression of senescence markers in NK subsets with
aging, 2. measure turnover rates in KIR+ and NKG2A+ NK cells from young and elderly adult subjects, 3.
evaluate the incidence of NK subpopulations with restricted receptor repertoire in young and elderly subjects
and will rigorously test whether the NK subpopulations are polyclonal or monoclonal. Our approach is
INNOVATIVE. We have documented a reciprocal relationship between NK receptors in aging and we have
demonstrated for the first time that NK subpopulations with restricted receptor repertoire are found in healthy
elderly people. It is our EXPECTATION that the proposed study will rigorously test our hypotheses and lead
to definitive future studies on NK subset development, function, proliferation, and senescence.
Status | Finished |
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Effective start/end date | 9/15/06 → 8/31/09 |
Funding
- National Institute on Aging: $118,388.00
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