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T Cell Homeostasis

Award Number: R01AI038903
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/1996
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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T Cell Homeostasis - Summary The durability of diverse forms of T cell memory is critical for effective immunity against various pathogens, and can be harnessed for cancer immunotherapy. Yet the signals that maintain T cell memory, and preserves the identity of distinct memory subsets, are incompletely understood. In particular, while there is considerable data suggesting that the cytokines IL-7 and IL-15 are important for preservation of memory CD8+ T cells, there are discrepancies in the literature that suggest this does not apply to all subpopulations of memory cells, or to all infectious systems. We believe some of these discrepancies arise from experimental procedures that do not accurately evaluate established memory T cell homeostasis (but which are conditioned by effects on memory generation). To test this, in Aim 1, we will use temporally inducible gene knockout strategies to eliminate sensitivity of T cells to IL-7 and/or IL-15, after the memory populations have been generated. We will examine these models in both steady-state T cell homeostasis and in the response to “bystander” infections. In Aim 2, we investigate the stability of two major classes of memory T cells – recirculating memory cells (“TMM”) and tissue-resident (“TRM”) cells. Each has different functional roles and distinct trafficking patterns. Based on published and preliminary studies, we will explore the role of the transcription factor KLF2 in controlling the “identity” of TMM vs TRM (and whether changes in KLF2 expression – by genetic manipulation or in response to statin drugs - will cause interconversion of TRM and TMM). We also investigate novel findings which indicate that expression of the egress factor S1PR1 (which is a gene regulated by KLF2) is critical for recirculation of TMM produced following some infections but not others, with consequences for therapeutic strategies to restain pathogenic T cell responses by targeting S1PR1. Again, these models will harness inducible gene knockout/expression models, as well as pharmacological treatments. Together, these studies represent a novel and highly significant investigation into the basis for durability in the diverse subpopulations of memory CD8+ T cells, with implications for how this can be manipulated for therapeutic goals.


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: 2025 ( Subtotal = $440,514 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	29	2/13/2025	NON-COMPETING CONTINUATION	$440,514
														Subtotal = $440,514

Issue Date FY: 2024 ( Subtotal = $458,912 )
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	28	12/22/2023	NON-COMPETING CONTINUATION	$413,021
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	001	28	5/24/2024	NON-COMPETING CONTINUATION	$45,891
														Subtotal = $458,912

Issue Date FY: 2023 ( Subtotal = $460,612 )
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	002	27	1/10/2023	NON-COMPETING CONTINUATION	$460,612
2023	2022	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	001	26	1/6/2023	COMPETING CONTINUATION	$31,386
2023	2020	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	25	1/6/2023	NON-COMPETING CONTINUATION	-$31,386
														Subtotal = $460,612

Issue Date FY: 2022 ( Subtotal = $464,177 )
2022	2022	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	001	26	2/11/2022	COMPETING CONTINUATION	$464,177
2022	2020	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	25	2/3/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $464,177

Issue Date FY: 2020 ( Subtotal = $378,474 )
2020	2020	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	25	6/12/2020	NON-COMPETING CONTINUATION	$378,474
														Subtotal = $378,474

Issue Date FY: 2019 ( Subtotal = $694,309 )
2019	2019	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	24	7/3/2019	NON-COMPETING CONTINUATION	$378,501
2019	2019	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	001	24	8/22/2019	NON-COMPETING CONTINUATION	$315,808
														Subtotal = $694,309

Issue Date FY: 2018 ( Subtotal = $378,528 )
2018	2018	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	23	6/8/2018	NON-COMPETING CONTINUATION	$378,528
														Subtotal = $378,528

Issue Date FY: 2017 ( Subtotal = $398,178 )
2017	2017	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	001	22	6/14/2017	NON-COMPETING CONTINUATION	$376,173
2017	2016	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	21	12/1/2016	COMPETING CONTINUATION	$22,005
														Subtotal = $398,178

Issue Date FY: 2016 ( Subtotal = $373,817 )
2016	2016	UNIVERSITY OF MINNESOTA, OFFICE OF STUDENT FINANCE AID	106 PLEASANT SE, 210 FRASER HL	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	21	5/9/2016	COMPETING CONTINUATION	$373,817
														Subtotal = $373,817

Issue Date FY: 2005 ( Subtotal = $289,263 )
2005	2005	UNIVERSITY OF MINNESOTA	UNIV GATEWAY#450/200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	10	5/26/2005	NON-COMPETING CONTINUATION	$289,263
														Subtotal = $289,263

Issue Date FY: 2004 ( Subtotal = $289,333 )
2004	2004	UNIVERSITY OF MINNESOTA	UNIV GATEWAY#450/200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	9	5/13/2004	NON-COMPETING CONTINUATION	$289,333
														Subtotal = $289,333

Issue Date FY: 2003 ( Subtotal = $289,401 )
2003	2003	UNIVERSITY OF MINNESOTA	UNIV GATEWAY#450/200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	8		NON-COMPETING CONTINUATION	$289,401
														Subtotal = $289,401

Issue Date FY: 2002 ( Subtotal = $289,468 )
2002	2002	UNIVERSITY OF MINNESOTA	UNIV GATEWAY#450/200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	7	5/13/2002	NON-COMPETING CONTINUATION	$289,468
														Subtotal = $289,468

Issue Date FY: 2001 ( Subtotal = $275,056 )
2001	2001	UNIVERSITY OF MINNESOTA	UNIV GATEWAY#450/200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Allergy and Infectious Diseases Research	000	6	5/18/2001	COMPETING CONTINUATION	$275,056
														Subtotal = $275,056

Grand Total All Awards = $5,480,042

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T Cell Homeostasis

Award Number: R01AI038903

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/1996

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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