This project is designed to discover important regulatory molecules that control T cell development within the thymus and peripheral immune responses. It is known that blood precursor cells appear in the embryonic region that will become the thymus at day 10/11 of embryogenesis in the mouse. These cells go through a series of developmental stages during which they acquire various capacities that will be eventually needed by the mature T cell to carry out appropriate immune functions. We have found that the thymic precursors undergo selective events medidated by caspases which are developmentally regulated and are essential to the process of programmed cell death. We have also found that Rlk, a protein tyrosine kinase, is representative of a novel class of tyrosine kinases that play an essential role in helping T cells to fight infections. These results may have important implications for bone marrow transplantation and immunodeficiency diseases involving T cells. - Thymus, differentiation, apoptosis, caspase, tyrosine kinase.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000627-08
Application #
6288899
Study Section
Special Emphasis Panel (LI)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Ozen, Ahmet; Comrie, William A; Ardy, Rico C et al. (2017) CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis. N Engl J Med 377:52-61
Schaeffer, E M; Debnath, J; Yap, G et al. (1999) Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity. Science 284:638-41
Jiang, D; Zheng, L; Lenardo, M J (1999) Caspases in T-cell receptor-induced thymocyte apoptosis. Cell Death Differ 6:402-11
Debnath, J; Chamorro, M; Czar, M J et al. (1999) rlk/TXK encodes two forms of a novel cysteine string tyrosine kinase activated by Src family kinases. Mol Cell Biol 19:1498-507