This proposal investigates a unique function for CDS T cells in the immune response against infectious agents. Our major focus is on the role that CDST cells play in the innate immune response during infection with Listeria monocytogenes (LM). We recently demonstrated that antigen non specific CDS T memory cells participate in a cytokine driven innate response against LM by secreting interferon-y. Further ransfer of """"""""innate"""""""" CDS T cells into interferon-y deficient mice protects them from infection with LM. We propose that CDST cells play a major role in the INF-y mediated innate response. In the first Aim we investigate the relative potency of CDS vs NK cells in providing this type of innate protection. We postulate that effector CDS T memory cells (TFM). which have been shown to play a minor role in the adaptive immune response play an important role in the innate response and will test thii hypothesis. In the second Aim we will examine the localization of CDS central memory cells (TOM). TEM. anc MK cells at sites of LM infection in spleen and liver. We will use mice deficient in CCR7 binding chemokine! CCL-19 and -21) to assess how this chemokine-receptor interaction affects CDS T cells in the innate response. We will also utilize new BAG transgenic mice that express Thy-1.1 as a reporter for IFN-y secretion to examine IFN-y secreting CDS and NK cells in situ. In the third Aim we will determine the role of CDS T cells in polarizing nai've CD4 T cells to the Th1 subset. In the fourth Aim we will examine by microarray analysis the gene display of CDS T cells that are activated by IL-12/18 (innate) vs those that are activated through the TcR (adaptive). In summary, this proposal will add important new information on how CDS T cells function in the innate immune response against intracellular pathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI045764-10
Application #
7743741
Study Section
Special Emphasis Panel (ZRG1-III (01))
Program Officer
Palker, Thomas J
Project Start
1999-09-01
Project End
2012-12-31
Budget Start
2010-01-01
Budget End
2012-12-31
Support Year
10
Fiscal Year
2010
Total Cost
$330,250
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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