Open Collections

The role of Cav1.4 calcium channel in T cell activation, proliferation, effector functions and death

University of British Columbia

T lymphocytes are an important part of the immune system that identify and destroy foreign antigens in the body as well as activate and deactivate other immune cells. In T lymphocytes, calcium is a secondary messenger that regulates activation and proliferation, effector function, survival and death. Although calcium release from the intracellular stores within T lymphocytes is well characterized, the calcium entry pathway from extracellular sources into T lymphocytes is unclear, despite contributing to the majority of elevated intracellular calcium ions during T lymphocyte activation. Preliminary studies have shown that L-type calcium channels play significant roles in the calcium influx pathways, mediating T lymphocyte activation and proliferation in vitro. Cav1.4 L-type calcium channel has been found to be expressed in both mouse and human T lymphocytes. To date, three Cav1.4 calcium channel splice variants have been identified with differential expression throughout the T lymphocyte proliferation process. I hypothesized that pore forming subunit of a L-type calcium channel, Cav1.4, regulates T lymphocyte activation and proliferation in vivo. To test this hypothesis, I used loss of function L-type calcium channel knock-out (KO) mice lacking the entire gene coding for this calcium channel and its splice variants to study its effects on T cell activation, proliferation, death, calcium uptake, and effector responses. From these studies, I predict that the lack of L-type calcium channels will cause T lymphocyte activation, proliferation and development to be impaired. These studies shed light on the mechanism of T lymphocyte activation and also enabled us to better understand how antagonistic drugs such as nifedipine may cause immunosuppressive effects.

Text

2011-06-06

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/35145

Microbiology and Immunology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/