Core C is central to the mission of the PPG since it will provide critical tools to PPG investigators for analyses of coinhibitory and costimulatory molecules to develop an understanding of the functions of positive and negative second signals in regulating T cell activation, tolerance and exhaustion. This Core will provide PPG investigators with an important and unique collection of mouse strains investigating the in vivo functions of T cell costimulatory/coinhibitory molecules individually, and their interplay. Core C has the expertise with both conventional and conditional transgenic and knockout technology that will enable the generation of novel mouse strains for analyzing the functions of immunoregulatory molecules in vivo.
Our specific aims are: 1) To generate novel knockout and transgenic mouse strains, conditionally or inducibly, 2) To generate mouse strains that facilitate analyses of the functions of coinhibitory/costimulatory molecules by breeding knockout mice with TCR transgenic or reporter mice, or analyses of interactions between coinhibitory receptors or interplay between positive and negative second signals by breeding various knockout mice with each other, 3) To maintain and provide mice of existing transgenic and knockout strains to PPG investigators. Core C will work closely with project investigators in all 3 projects, not only to provide them with transgenic and knockout strains, but also to generate novel strains based upon their findings in PPG projects. Core C also will provide knockout mice to Core B for immunization to generate novel mAbs. Taken together, these activities of Core C will provide PPG investigators with novel mouse strains for studying the roles of costimulatory and coinhibitory molecules in controlling T cell responses in mouse models of graft-versus-host disease, autoimmunity, and infection.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
2P01AI056299-11
Application #
8742090
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Harvard Medical School
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
Flynn, Ryan; Du, Jing; Veenstra, Rachelle G et al. (2014) Increased T follicular helper cells and germinal center B cells are required for cGVHD and bronchiolitis obliterans. Blood 123:3988-98
Penaloza-MacMaster, Pablo; Kamphorst, Alice O; Wieland, Andreas et al. (2014) Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection. J Exp Med 211:1905-18
Sawitzki, Birgit; Brunstein, Claudio; Meisel, Christian et al. (2014) Prevention of graft-versus-host disease by adoptive T regulatory therapy is associated with active repression of peripheral blood Toll-like receptor 5 mRNA expression. Biol Blood Marrow Transplant 20:173-82
Dubovsky, Jason A; Flynn, Ryan; Du, Jing et al. (2014) Ibrutinib treatment ameliorates murine chronic graft-versus-host disease. J Clin Invest 124:4867-76
Xiao, Yanping; Yu, Sanhong; Zhu, Baogong et al. (2014) RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance. J Exp Med 211:943-59
Porichis, Filippos; Hart, Meghan G; Zupkosky, Jennifer et al. (2014) Differential impact of PD-1 and/or interleukin-10 blockade on HIV-1-specific CD4 T cell and antigen-presenting cell functions. J Virol 88:2508-18
Mott, Kevin R; Allen, Sariah J; Zandian, Mandana et al. (2014) Inclusion of CD80 in HSV targets the recombinant virus to PD-L1 on DCs and allows productive infection and robust immune responses. PLoS One 9:e87617
Joller, Nicole; Lozano, Ester; Burkett, Patrick R et al. (2014) Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses. Immunity 40:569-81
Alexander, Kylie A; Flynn, Ryan; Lineburg, Katie E et al. (2014) CSF-1-dependant donor-derived macrophages mediate chronic graft-versus-host disease. J Clin Invest 124:4266-80
Ding, Zhi-Chun; Lu, Xiaoyun; Yu, Miao et al. (2014) Immunosuppressive myeloid cells induced by chemotherapy attenuate antitumor CD4+ T-cell responses through the PD-1-PD-L1 axis. Cancer Res 74:3441-53

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