CTLA-4 . FasL induces early apoptosis of activated T cells by interfering with anti-apoptotic signals.
Publication/Presentation Date
12-1-2007
Abstract
The fusion protein CTLA-4 . FasL, a paradigmatic "trans signal converter protein", can attach to APC surfaces and in effect convert B7-activating costimulator signals into inhibitory Fas receptor-generated signals. The present study investigates CTLA-4 . FasL's mechanism of action. A combination of p27(kip) and proliferating cell nuclear Ag Western blot and propidium iodide flow cytometric analysis showed no CTLA-4 . FasL effect on cell cycle entry and progression, pointing away from the kind of classical anergy associated with CTLA-4 . Ig. Significantly, CTLA-4 . FasL elicited apoptosis (as detected by annexin-V/propidium iodide costaining) as early as 24 h after T cell activation, suggesting that some coordinate signaling might be capacitating the Fas receptor. Significantly, CTLA-4 . FasL, but not CTLA-4 . Ig, anti-Fas mAb, or the two in combination, abrogated the usual increase in expression of the anti-apototic protein, cFLIP. Furthermore, activation of caspases 8 and 3 were not affected by CTLA-4 . FasL. These findings suggest a model for CTLA-4 . FasL action wherein there is coordinate triggering of a death receptor and suppression of a proapoptotic protein.
Volume
179
Issue
11
First Page
7287
Last Page
7294
ISSN
0022-1767
Published In/Presented At
Orbach, A., Rachmilewitz, J., Parnas, M., Huang, J. H., Tykocinski, M. L., & Dranitzki-Elhalel, M. (2007). CTLA-4 . FasL induces early apoptosis of activated T cells by interfering with anti-apoptotic signals. Journal of immunology (Baltimore, Md. : 1950), 179(11), 7287–7294. https://doi.org/10.4049/jimmunol.179.11.7287
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
18025171
Department(s)
Administration and Leadership
Document Type
Article