A fundamental issue in immunology is the fate of naive T-cells after stimulation by antigens. Accumulating data from many laboratories, including that of the principal investigator, in the last several decades have established that costimulatory signal is critical in determining whether T-cells will be activated or inactivated when the T-cell receptors are engaged by antigen. More recently, it has been shown by the principal investigator and others that costimulatory molecules also determine differentiation of T-cells after antigenic stimulation. They have demonstrated that distinct costimulatory molecules such as B7 and the heat-stable antigen (HSA) play distinct roles in the induction of two major products of T-cell response: effector and memory T-cells. The long-term goal of this research program remains to elucidate the role of multiple costimulatory molecules in T-cell activation. The current application focus on the mechanisms by which multiple costimulatory pathways participate in the induction of memory and effector CTL. First, using mice with targeted mutation of either HSA or CD28, the investigators will determine the mechanisms by which these costimulatory molecules promote the induction of memory and effector T-cells. Second, they will carry out lineage-ablation experiments to test whether effector T-cells are precursors of memory T-cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI032981-09
Application #
6373277
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Cairns, Scott
Project Start
1994-05-01
Project End
2003-04-30
Budget Start
2001-05-01
Budget End
2003-04-30
Support Year
9
Fiscal Year
2001
Total Cost
$221,320
Indirect Cost
Name
Ohio State University
Department
Pathology
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Bai, Xue-Feng; Li, Ou; Zhou, Qunmin et al. (2004) CD24 controls expansion and persistence of autoreactive T cells in the central nervous system during experimental autoimmune encephalomyelitis. J Exp Med 200:447-58
Liu, Xingluo; Gao, Jian Xin; Wen, Jing et al. (2003) B7DC/PDL2 promotes tumor immunity by a PD-1-independent mechanism. J Exp Med 197:1721-30
Gao, Jian-Xin; Liu, Xingluo; Wen, Jing et al. (2003) Two-signal requirement for activation and effector function of natural killer cell response to allogeneic tumor cells. Blood 102:4456-63
Bai, Xue-Feng; Liu, Jinqing; Li, Ou et al. (2003) Antigenic drift as a mechanism for tumor evasion of destruction by cytolytic T lymphocytes. J Clin Invest 111:1487-96
Gao, Jian-Xin; Liu, Xingluo; Wen, Jing et al. (2003) Differentiation of monocytic cell clones into CD8 alpha+ dendritic cells (DC) suggests that monocytes can be direct precursors for both CD8 alpha+ and CD8 alpha- DC in the mouse. J Immunol 170:5927-35
Gao, Jian-Xin; Zhang, Huiming; Bai, Xue-Feng et al. (2002) Perinatal blockade of b7-1 and b7-2 inhibits clonal deletion of highly pathogenic autoreactive T cells. J Exp Med 195:959-71
Bai, X F; Gao, J X; Liu, J et al. (2001) On the site and mode of antigen presentation for the initiation of clonal expansion of CD8 T cells specific for a natural tumor antigen. Cancer Res 61:6860-7
Guilloux, Y; Bai, X F; Liu, X et al. (2001) Optimal induction of effector but not memory antitumor cytotoxic T lymphocytes involves direct antigen presentation by the tumor cells. Cancer Res 61:1107-12
Liu, X; Bai, X F; Wen, J et al. (2001) B7H costimulates clonal expansion of, and cognate destruction of tumor cells by, CD8(+) T lymphocytes in vivo. J Exp Med 194:1339-48
Liu, Y; Zheng, P (2001) Is tumor expression of the major histocompatibility complex antigen required for T cell immune surveillance? Arch Immunol Ther Exp (Warsz) 49 Suppl 2:S61-4

Showing the most recent 10 out of 21 publications