The long-term goal of the proposed research is to examine how biochemical signaling changes determine effector and memory generation and function. Understanding the mechanisms whereby memory immune cells are generated and maintained is central to developing therapies to enhance memory responses in vaccine design and eliminate memory cell function in autimmune diseases. Our central hypothesis is that distinct signaling pathways initiated at the T cell Receptor control the generation and function of effector and memory CD4 T cells. Proposed are experiments designed to examine the mechanisms by which activation signals initiated at the TCR are coupled to downstream signaling intermediates resulting in the distinct function of effector and memory T cells.
The specific aims for the proposed research include defining the roles of FcR gamma and Syk in effector T cell signaling and function, analyzing differential TCR-mediated signaling in effector and memory CENT cells, and determining the membrane organization of signaling intermediates in naive, effector and memory CD4 T cells. Characterizing the signaling pathways of these T cell subsets may lead to the identification of molecular targets for immunomodulation of T cell function. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI058924-03
Application #
7029714
Study Section
Special Emphasis Panel (ZRG1-MBC-1 (29))
Program Officer
Hernandez, Milton J
Project Start
2004-03-16
Project End
2007-03-15
Budget Start
2006-03-16
Budget End
2007-03-15
Support Year
3
Fiscal Year
2006
Total Cost
$27,758
Indirect Cost
Name
University of Maryland Baltimore
Department
Surgery
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Okoye, Francesca I; Krishnan, Sandeep; Chandok, Meena R et al. (2007) Proximal signaling control of human effector CD4 T cell function. Clin Immunol 125:5-15