Abstract
The Bcl-2-associated X protein (Bax) and Bcl-2-antagonist/killer (Bak) are essential regulators of lymphocyte apoptosis, but whether they play a role in viable T cell function remains unclear. Here, we report that T cells lacking both Bax and Bak display defects in antigen-specific proliferation because of Ca2+-signaling defects. Bax-/-, Bak-/- T cells displayed defective T cell receptor (TCR)- and inositol-1,4,5-trisphosphate (IP3)-dependent Ca2+ mobilization because of altered endoplasmic reticulum (ER) Ca2+ regulation that was reversed by Bax's reintroduction. The ability of TCR-dependent Ca2+ signals to stimulate mitochondrial NADH production in excess of that utilized for ATP synthesis was dependent on Bax and Bak. Blunting of Ca2+-induced mitochondrial NADH elevation in the absence of Bax and Bak resulted in decreased reactive-oxygen-species production, which was required for T cell proliferation. Together, the data establish that Bax and Bak play an essential role in the control of T cell proliferation by modulating ER Ca2+ release.
Original language | English (US) |
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Pages (from-to) | 268-280 |
Number of pages | 13 |
Journal | Immunity |
Volume | 27 |
Issue number | 2 |
DOIs | |
State | Published - Aug 24 2007 |
Externally published | Yes |
Keywords
- MOLIMMUNO
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases