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 that enable studies of 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, as well as CRISPR/Cas9 engineering, which 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 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 in controlling T cell responses in mouse models of infection, autoimmunity, cancer and chronic graft-versus-host disease.
Core C will make genetically engineered mouse strains for use by Program investigators in experimental models of infection, autoimmunity, cancer and transplantation. These mouse strains will be useful tools for identifying mechanisms that regulate immune responses, and guiding translation to new therapies for human diseases. .
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| Porichis, Filippos; Hart, Meghan G; Massa, Alexandra et al. (2018) Immune Checkpoint Blockade Restores HIV-Specific CD4 T Cell Help for NK Cells. J Immunol 201:971-981 |
| LaFleur, Martin W; Muroyama, Yuki; Drake, Charles G et al. (2018) Inhibitors of the PD-1 Pathway in Tumor Therapy. J Immunol 200:375-383 |
| Chaudhri, Apoorvi; Xiao, Yanping; Klee, Alyssa N et al. (2018) PD-L1 Binds to B7-1 Only In Cis on the Same Cell Surface. Cancer Immunol Res 6:921-929 |
| Ahn, Eunseon; Araki, Koichi; Hashimoto, Masao et al. (2018) Role of PD-1 during effector CD8 T cell differentiation. Proc Natl Acad Sci U S A 115:4749-4754 |
| Wu, Yongxia; Schutt, Steven; Paz, Katelyn et al. (2018) MicroRNA-17-92 is required for T-cell and B-cell pathogenicity in chronic graft-versus-host disease in mice. Blood 131:1974-1986 |
| Gartlan, Kate H; Bommiasamy, Hemamalini; Paz, Katelyn et al. (2018) A critical role for donor-derived IL-22 in cutaneous chronic GVHD. Am J Transplant 18:810-820 |
| Hippen, Keli L; Loschi, Michael; Nicholls, Jemma et al. (2018) Effects of MicroRNA on Regulatory T Cells and Implications for Adoptive Cellular Therapy to Ameliorate Graft-versus-Host Disease. Front Immunol 9:57 |
| Newton, Ryan H; Shrestha, Sharad; Sullivan, Jenna M et al. (2018) Maintenance of CD4 T cell fitness through regulation of Foxo1. Nat Immunol 19:838-848 |
| Owen, David L; Mahmud, Shawn A; Vang, Kieng B et al. (2018) Identification of Cellular Sources of IL-2 Needed for Regulatory T Cell Development and Homeostasis. J Immunol 200:3926-3933 |
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