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NK T Cell Interactions with NK Cells During Viral Infection

Award Number: R01AI046709
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

Murine cytomegalovirus (MCMV), the mouse homolog of human CMV, is a well- characterized model system for the study of CMV infection in a mammalian host. There is a growing interest in the anti-viral role of MHC class Ib-restricted T cells, referred to as non- classical T cells. During the previous funding period, using mice deficient in conventional CD8+ T cells or CD1d-restricted NKT cells, we showed that non-classical T cells contribute significantly to the immune response to MCMV infection. Our preliminary data also demonstrate that a subset of non-classical CD8+ T cells, likely restricted by the Qa-1 molecule, is sufficient to protect against MCMV induced lethality. We therefore hypothesized that non-classical T cells may substitute for NK cells and conventional T cells when their effector responses are impaired during viral immuno-evasion. The objective of this proposal is to understand how non-classical T cells contribute to the immune response to viral infections. To accomplish these goals, we generated and acquired a variety of unique tools and animal models. These include KbDbQa-1 deficient animals, a new Ja18-/- mouse line, an MCMV open reading frame library, and a large number of MCMV mutants. In Specific Aim 1, we will define MCMV specific Qa-1 restricted CD8+ T cells and identify the MCMV peptide(s) they recognize. In Specific Aim 2, we propose to investigate the role of CD1d, Qa-2 and M3 restricted T cells during MCMV infection. This proposal fills a major gap in our understanding of the role of non-classical T cells during viral infection. The results from these studies are likely to have relevance to infections caused by other viruses and aid in the design of strategies directed at manipulating non-classical T cells.


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: 2024 ( Subtotal = $0 )
2024	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	19	3/21/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $699,391 )
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	19	4/28/2022	NON-COMPETING CONTINUATION	$618,272
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	001	19	4/29/2022	SUPPLEMENT FOR EXPANSION	$81,119
														Subtotal = $699,391

Issue Date FY: 2021 ( Subtotal = $686,266 )
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	001	18	7/20/2021	SUPPLEMENT FOR EXPANSION	$67,994
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	18	3/23/2021	NON-COMPETING CONTINUATION	$618,272
														Subtotal = $686,266

Issue Date FY: 2020 ( Subtotal = $618,272 )
2020	2020	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	17	3/24/2020	NON-COMPETING CONTINUATION	$618,272
														Subtotal = $618,272

Issue Date FY: 2019 ( Subtotal = $618,272 )
2019	2019	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	16	3/22/2019	NON-COMPETING CONTINUATION	$618,272
														Subtotal = $618,272

Issue Date FY: 2018 ( Subtotal = $618,272 )
2018	2018	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	002	15	8/8/2018	COMPETING CONTINUATION	$125,899
2018	2018	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	004	15	9/21/2018	COMPETING CONTINUATION	$22,834
2018	2018	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	001	15	5/7/2018	COMPETING CONTINUATION	$492,373
2018	2016	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	003	14	9/21/2018	EXTENSION WITH OR WITHOUT FUNDS	-$22,834
2018	2016	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	14	5/4/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $618,272

Issue Date FY: 2016 ( Subtotal = $397,058 )
2016	2016	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	14	7/7/2016	EXTENSION WITH OR WITHOUT FUNDS	$397,058
														Subtotal = $397,058

Issue Date FY: 2015 ( Subtotal = $397,058 )
2015	2015	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	13	6/22/2015	NON-COMPETING CONTINUATION	$397,058
														Subtotal = $397,058

Issue Date FY: 2014 ( Subtotal = $397,058 )
2014	2014	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	12	7/2/2014	NON-COMPETING CONTINUATION	$397,058
														Subtotal = $397,058

Issue Date FY: 2013 ( Subtotal = $373,234 )
2013	2013	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	002	11	8/8/2013	COMPETING CONTINUATION	$373,234
2013	2011	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	10	6/15/2013	NON-COMPETING CONTINUATION	$0
2013	2011	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	001	10	8/6/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $373,234

Issue Date FY: 2011 ( Subtotal = $384,329 )
2011	2011	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	10	7/8/2011	NON-COMPETING CONTINUATION	$384,329
														Subtotal = $384,329

Issue Date FY: 2010 ( Subtotal = $656,946 )
2010	2010	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Trans-NIH Recovery Act Research Support	001	9	8/11/2010	SUPPLEMENT FOR EXPANSION	$254,810
2010	2010	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	9	6/18/2010	NON-COMPETING CONTINUATION	$402,136
														Subtotal = $656,946

Issue Date FY: 2009 ( Subtotal = $421,205 )
2009	2009	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	7	4/22/2009	SUPPLEMENT FOR EXPANSION	$14,793
2009	2009	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	001	8	6/29/2009	NON-COMPETING CONTINUATION	$406,412
														Subtotal = $421,205

Issue Date FY: 2008 ( Subtotal = $343,882 )
2008	2008	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	7	6/26/2008	NON-COMPETING CONTINUATION	$343,882
														Subtotal = $343,882

Issue Date FY: 2007 ( Subtotal = $350,752 )
2007	2007	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	6	7/5/2007	COMPETING CONTINUATION	$350,752
														Subtotal = $350,752

Issue Date FY: 2005 ( Subtotal = $230,767 )
2005	2005	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	5	2/11/2005	NON-COMPETING CONTINUATION	$230,767
														Subtotal = $230,767

Issue Date FY: 2004 ( Subtotal = $230,905 )
2004	2004	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	4	2/19/2004	NON-COMPETING CONTINUATION	$230,905
														Subtotal = $230,905

Issue Date FY: 2003 ( Subtotal = $231,039 )
2003	2003	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	3		NON-COMPETING CONTINUATION	$231,039
														Subtotal = $231,039

Issue Date FY: 2002 ( Subtotal = $231,169 )
2002	2002	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	2	3/11/2002	NON-COMPETING CONTINUATION	$231,169
														Subtotal = $231,169

Issue Date FY: 2001 ( Subtotal = $117,938 )
2001	2001	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Allergy and Infectious Diseases Research	000	1	2/12/2001	NEW	$117,938
														Subtotal = $117,938

Grand Total All Awards = $8,003,813

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NK T Cell Interactions with NK Cells During Viral Infection

Award Number: R01AI046709

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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