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Defective Th function induced by a dominant-negative cAMP response element binding protein mutation is reversed by
F Zhang1, M Rincon, R A Flavell
1Division of Rheumatology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37025, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|August 5, 2000
Summary
cAMP response element binding protein (CREB) is vital for T helper cell function. Inhibiting CREB impairs T helper cell responses and increases cell death, highlighting its role in adaptive immunity.
Area of Science:
- Immunology
- Molecular Biology
Background:
- cAMP response element binding protein (CREB) regulates gene expression in response to stimuli.
- CREB is induced in T cell precursors but its role in mature T cells is unclear.
Purpose of the Study:
- To define the role of CREB in mature T cell function and adaptive immunity.
Main Methods:
- Utilized transgenic mice with a CREB dominant-negative (dn) mutation in T cells.
- Assessed T cell development, homeostasis, expansion, in vitro/in vivo function, and activation-induced cell death.
- Investigated the role of BCL-2 in CREB-mediated T cell function.
Main Results:
- CREB-dn T cells showed normal development and homeostasis but impaired function and increased susceptibility to activation-induced cell death.
- CREB-dn T cells had reduced BCL-2 levels.
- BCL-2 overexpression rescued CREB-dn T cell function and reduced cell death.
Conclusions:
- CREB is critical for T helper cell function and adaptive immune responses.
- CREB regulates T cell survival by inhibiting stimulus-dependent cell death, partly through BCL-2 modulation.