Tuesday, December 23, 2025 12/23/2025

Dysregulation of Naïve T cell Quiescence during Aging

Award Number: K01AG068373
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/26/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Dysregulation of Naïve T cell Quiescence during Aging - Project Summary/Abstract A common feature of human aging is an increased susceptibility to infections. This age-related susceptibility is linked with a significant and reproducible loss of naïve T cells in older individuals. Notably, aged naïve cells not only reduce in number but also display features of partial differentiation, implying a loss in cellular quiescence may cause repertoire contraction and dysfunction with age. Naïve T cell quiescence is classically maintained within secondary lymphoid tissues (SLTs) by fibroblastic reticular cells (FRCs). Mouse models have elegantly demonstrated the ability of FRCs to promote T cell survival and directly inhibit activation-induced differentiation. These data suggest that FRCs actively regulate naïve T cell quiescence and likely play an essential role in its loss during aging. However, mechanistic studies in humans are significantly confounded by rare use of single cell technologies and limited by poor naïve T cell survival in standard in vitro culture and humanized mice. Better utilization of new single cell techniques and the development of novel methodologies that sustain naïve T cells in vitro is thus required to gain further insight into naïve T cell maintenance during human aging. Our preliminary data suggests high heterogeneity of human naïve T cells that narrows with age, a situation that can be mimicked in vitro through the use of a novel SLT-like organoid model system. For this proposal, Aim 1 will define the overall phenotypic, transcriptional and epigenetic heterogeneity of the naïve T cell compartment during human aging. In addition, Aim 2 will further develop SLT-like organoids for the long- term study of naïve T cell quiescence. Aim 3 will use our organoid system, in combination with ex vivo and in vitro assays, to determine the role of FRCs in the maintenance of naïve T cell quiescence and its breakdown with aging. The overarching goals of these studies are to define fundamental naïve T cell heterogeneity and determine causes of age-related homeostatic decline – to ultimately identify potential therapeutic interventions to boost protective immunity and prevent pathogenic infections in older individuals. The applicant Dr. Claire Gustafson has outlined an integrative five-year research and career development plan to advance her knowledge in single cell techniques and their analysis pipelines and to develop a novel, organoid-based research platform to study T cell homeostasis during aging. Dr. Gustafson’s mentor, Dr. Jörg Goronzy, has comprehensive expertise in T cell aging as well as an extensive network of scientific collaborators using high throughput analytical techniques. This mentorship combined with Dr. Gustafson’s team of expert advisors and the resources available at Stanford University provides an exceptional research environment for Dr. Gustafson to successfully become a strong independent investigator in the area of human immune aging.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2024	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Aging Research	000	6	12/1/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $126,252 )
2024	2024	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Aging Research	000	6	5/14/2024	NON-COMPETING CONTINUATION	$126,252
														Subtotal = $126,252

Issue Date FY: 2023 ( Subtotal = $126,252 )
2023	2023	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Aging Research	000	5	5/17/2023	NON-COMPETING CONTINUATION	$126,252
														Subtotal = $126,252

Issue Date FY: 2022 ( Subtotal = $126,252 )
2022	2022	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Aging Research	003	4	7/7/2022	NON-COMPETING CONTINUATION	$126,252
2022	2021	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Aging Research	002	3	11/19/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$29,231
2022	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	001	2	11/19/2021	NON-COMPETING CONTINUATION	-$19,820
2022	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	000	1	11/19/2021	NEW	-$9,411
														Subtotal = $126,252

Issue Date FY: 2021 ( Subtotal = $126,252 )
2021	2021	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Aging Research	002	3	9/7/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$106,432
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	000	2	7/8/2021	NON-COMPETING CONTINUATION	$126,252
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	001	2	9/3/2021	NON-COMPETING CONTINUATION	-$106,432
														Subtotal = $126,252

Issue Date FY: 2020 ( Subtotal = $126,252 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	000	1	7/30/2020	NEW	$126,252
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Aging Research	001	1	8/7/2020	NEW	$0
														Subtotal = $126,252

Grand Total All Awards = $631,260

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Dysregulation of Naïve T cell Quiescence during Aging

Award Number: K01AG068373

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/26/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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