Abstract

The long term goal of this application is to study the role of peptides in shaping the repertoire of T-cells selected in the thymus. Towards this end, the investigator will utilize a novel mouse strain that expresses a single self peptide (CLIP) bound to all of its class II molecules (H2-M deficient mice). Most interesting, preliminary studies have shown that these mice display a very heterogenous T-cell repertoire and are highly autoreactive. These mice will be utilized to determine the precursor frequency of autoreactive T-cells, to analyze effector function of CD4+ T-cells that mature in such an environment, and to test the tolerogenicity of cortical thymic epithelial cells. An understanding of these processes is critical for understanding the mechanisms involved in thymic selection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI041079-04
Application #
6170412
Study Section
Immunobiology Study Section (IMB)
Program Officer
Ridge, John P
Project Start
1997-09-01
Project End
2002-08-31
Budget Start
2000-09-01
Budget End
2002-08-31
Support Year
4
Fiscal Year
2000
Total Cost
$221,744
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Davey, Gayle M; Starr, Robyn; Cornish, Ann L et al. (2005) SOCS-1 regulates IL-15-driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential. J Exp Med 202:1099-108
Surh, Charles D; Sprent, Jonathan (2005) Regulation of mature T cell homeostasis. Semin Immunol 17:183-91
Kieper, William C; Troy, Amy; Burghardt, J Theodore et al. (2005) Recent immune status determines the source of antigens that drive homeostatic T cell expansion. J Immunol 174:3158-63
Kieper, William C; Burghardt, J Theodore; Surh, Charles D (2004) A role for TCR affinity in regulating naive T cell homeostasis. J Immunol 172:40-4
Kondrack, Robyn M; Harbertson, Judith; Tan, Joyce T et al. (2003) Interleukin 7 regulates the survival and generation of memory CD4 cells. J Exp Med 198:1797-806
Sprent, Jonathan; Surh, Charles D (2003) Cytokines and T cell homeostasis. Immunol Lett 85:145-9
Rosen, Hugh; Alfonso, Christopher; Surh, Charles D et al. (2003) Rapid induction of medullary thymocyte phenotypic maturation and egress inhibition by nanomolar sphingosine 1-phosphate receptor agonist. Proc Natl Acad Sci U S A 100:10907-12
Tan, Joyce T; Ernst, Bettina; Kieper, William C et al. (2002) Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells. J Exp Med 195:1523-32
Zhang, Xiaohong; Fujii, Hideki; Kishimoto, Hidehiro et al. (2002) Aging leads to disturbed homeostasis of memory phenotype CD8(+) cells. J Exp Med 195:283-93
Judge, Adam D; Zhang, Xiaohong; Fujii, Hideki et al. (2002) Interleukin 15 controls both proliferation and survival of a subset of memory-phenotype CD8(+) T cells. J Exp Med 196:935-46

Showing the most recent 10 out of 17 publications