Abstract

In this application, Dr. Mescher proposes to continue his studies identifying ligands that are essential for the activation of naive and memory cytotoxic T lymphocytes. Utilizing both his pioneering system of artificial surfaces for the delivery of defined signals and an adoptive transfer of CTLs from transgenic TCR mice, Dr. Mescher proposes to confirm much of his preliminary work identifying the key signals responsible for triggering CTL activation. This renewal application is expanded to include experiments to define the potential role that IL-12 plays in activating the naive CTL response as well as investigating a potential role for inflammatory cytokines in influencing memory cell function.
Two specific aims, which are essentially identical to the specific aims of the original project, with the important addition of the adoptive transgenic mouse system are proposed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI034824-07
Application #
6124277
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Quill, Helen R
Project Start
1993-07-01
Project End
2003-11-30
Budget Start
1999-12-01
Budget End
2000-11-30
Support Year
7
Fiscal Year
2000
Total Cost
$201,498
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Pathology
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Gerner, Michael Y; Heltemes-Harris, Lynn M; Fife, Brian T et al. (2013) Cutting edge: IL-12 and type I IFN differentially program CD8 T cells for programmed death 1 re-expression levels and tumor control. J Immunol 191:1011-5
Curtsinger, Julie M; Agarwal, Pujya; Lins, Debra C et al. (2012) Autocrine IFN-ýý promotes naive CD8 T cell differentiation and synergizes with IFN-ýý to stimulate strong function. J Immunol 189:659-68
Curtsinger, Julie M; Mescher, Matthew F (2010) Inflammatory cytokines as a third signal for T cell activation. Curr Opin Immunol 22:333-40
Gerner, Michael Y; Mescher, Matthew F (2009) Antigen processing and MHC-II presentation by dermal and tumor-infiltrating dendritic cells. J Immunol 182:2726-37
Agarwal, Pujya; Raghavan, Arvind; Nandiwada, Sarada L et al. (2009) Gene regulation and chromatin remodeling by IL-12 and type I IFN in programming for CD8 T cell effector function and memory. J Immunol 183:1695-704
Xiao, Zhengguo; Casey, Kerry A; Jameson, Stephen C et al. (2009) Programming for CD8 T cell memory development requires IL-12 or type I IFN. J Immunol 182:2786-94
Hammerbeck, Christopher D; Mescher, Matthew F (2008) Antigen controls IL-7R alpha expression levels on CD8 T cells during full activation or tolerance induction. J Immunol 180:2107-16
Gerner, Michael Y; Casey, Kerry A; Mescher, Matthew F (2008) Defective MHC class II presentation by dendritic cells limits CD4 T cell help for antitumor CD8 T cell responses. J Immunol 181:155-64
Casey, Kerry A; Mescher, Matthew F (2007) IL-21 promotes differentiation of naive CD8 T cells to a unique effector phenotype. J Immunol 178:7640-8
Xiao, Zhengguo; Curtsinger, Julie M; Prlic, Martin et al. (2007) The CD8 T cell response to vaccinia virus exhibits site-dependent heterogeneity of functional responses. Int Immunol 19:733-43

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