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)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
2P01AI056299-11
Application #
8742090
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-09-01
Budget End
2015-08-31
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
Xu, Jie; Sun, Heather H; Fletcher, Christopher D M et al. (2016) Expression of Programmed Cell Death 1 Ligands (PD-L1 and PD-L2) in Histiocytic and Dendritic Cell Disorders. Am J Surg Pathol 40:443-53
Borges, Christopher M; Reichenbach, Dawn K; Kim, Beom Seok et al. (2016) Regulatory T cell expressed MyD88 is critical for prolongation of allograft survival. Transpl Int 29:930-40
Chapuy, Bjoern; Roemer, Margaretha G M; Stewart, Chip et al. (2016) Targetable genetic features of primary testicular and primary central nervous system lymphomas. Blood 127:869-81
Schildberg, Frank A; Klein, Sarah R; Freeman, Gordon J et al. (2016) Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family. Immunity 44:955-72
Schönle, Anne; Hartl, Frederike A; Mentzel, Jan et al. (2016) Caveolin-1 regulates TCR signal strength and regulatory T-cell differentiation into alloreactive T cells. Blood 127:1930-9
Flynn, Ryan; Paz, Katelyn; Du, Jing et al. (2016) Targeted Rho-associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism. Blood 127:2144-54
Zeiser, Robert; Blazar, Bruce R (2016) Preclinical models of acute and chronic graft-versus-host disease: how predictive are they for a successful clinical translation? Blood 127:3117-26
Hirakawa, Masahiro; Matos, Tiago; Liu, Hongye et al. (2016) Low-dose IL-2 selectively activates subsets of CD4(+) Tregs and NK cells. JCI Insight 1:e89278
Li, Wei; Liu, Liangyi; Gomez, Aurelie et al. (2016) Proteomics analysis reveals a Th17-prone cell population in presymptomatic graft-versus-host disease. JCI Insight 1:
Lo, Tsun-Ho; Silveira, Pablo A; Fromm, Phillip D et al. (2016) Characterization of the Expression and Function of the C-Type Lectin Receptor CD302 in Mice and Humans Reveals a Role in Dendritic Cell Migration. J Immunol 197:885-98

Showing the most recent 10 out of 257 publications