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 #
5R01AI045764-08
Application #
7332218
Study Section
Special Emphasis Panel (ZRG1-III (01))
Program Officer
Palker, Thomas J
Project Start
1999-09-01
Project End
2010-12-31
Budget Start
2008-01-01
Budget End
2008-12-31
Support Year
8
Fiscal Year
2008
Total Cost
$333,563
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
Mandraju, Rajakumar; Murray, Sean; Forman, James et al. (2014) Differential ability of surface and endosomal TLRs to induce CD8 T cell responses in vivo. J Immunol 192:4303-15
Chowdhury, Fatema Z; Estrada, Leonardo D; Murray, Sean et al. (2014) Pharmacological inhibition of TPL2/MAP3K8 blocks human cytotoxic T lymphocyte effector functions. PLoS One 9:e92187
Chowdhury, Fatema Z; Ramos, Hilario J; Davis, Laurie S et al. (2011) IL-12 selectively programs effector pathways that are stably expressed in human CD8+ effector memory T cells in vivo. Blood 118:3890-900
Sieve, Amy N; Meeks, Karen D; Lee, Suheung et al. (2010) A novel immunoregulatory function for IL-23: Inhibition of IL-12-dependent IFN-ýý production. Eur J Immunol 40:2236-47
Toneff, Michael J; Du, Zhijun; Dong, Jie et al. (2010) Somatic expression of PyMT or activated ErbB2 induces estrogen-independent mammary tumorigenesis. Neoplasia 12:718-26
Ramos, Hilario J; Davis, Ann M; Cole, Alexander G et al. (2009) Reciprocal responsiveness to interleukin-12 and interferon-alpha specifies human CD8+ effector versus central memory T-cell fates. Blood 113:5516-25
Sinai, Parisa; Berg, Rance E; Haynie, J Marshall et al. (2007) Imatinib mesylate inhibits antigen-specific memory CD8 T cell responses in vivo. J Immunol 178:2028-37
Berg, Rance E; Forman, James (2006) The role of CD8 T cells in innate immunity and in antigen non-specific protection. Curr Opin Immunol 18:338-43
Berg, Rance E; Crossley, Emily; Murray, Sean et al. (2005) Relative contributions of NK and CD8 T cells to IFN-gamma mediated innate immune protection against Listeria monocytogenes. J Immunol 175:1751-7
Gunturi, Anasuya; Berg, Rance E; Crossley, Emily et al. (2005) The role of TCR stimulation and TGF-beta in controlling the expression of CD94/NKG2A receptors on CD8 T cells. Eur J Immunol 35:766-75

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