T lymphocytes play a critical role in host defense against microbes and cancer. A remarkable feature of the signals that trigger T cell participation in the immune response is that every cell appears to have a mandate that assures its daughters will not uniformly adopt the same fate. This proposal develops novel methodologies to image the characteristics of dividing T cells during the course of an infectious disease.
The aims of the project are to test the importance of unequal cellular inheritance in the earliest stages of the immune response, where an abundance of cell fate decisions are being made (Aim 1), in the re-challenge response wherein memory T cells may be mimicking the regenerative behavior of adult stem cells (Aim 2), and in chronic infection because this scenario may tax the regenerative limits of normal memory T cells (Aim 3). The studies proposed herein should offer novel approaches for maintaining lifelong immunity against chronic infections and for eliminating many life-threatening infectious diseases.

Public Health Relevance

T lymphocytes are specialized white blood cells that protect us against infection. These cells need to be able to perform an assortment of functions and to replenish themselves for us to survive in a germ-filled world. This project will provide important information about how these cells can fight off different kinds of germs over the course of our lifetime.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI113365-01
Application #
8767544
Study Section
Immunity and Host Defense Study Section (IHD)
Program Officer
Kelly, Halonna R
Project Start
2014-06-01
Project End
2019-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$400,000
Indirect Cost
$150,000
Name
Columbia University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Chaix, Julie; Nish, Simone A; Lin, Wen-Hsuan W et al. (2014) Cutting edge: CXCR4 is critical for CD8+ memory T cell homeostatic self-renewal but not rechallenge self-renewal. J Immunol 193:1013-6