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Dissecting T Cell Contraction In Vivo Using a Genetically Encoded Reporter of Apoptosis

Authors :
Garrod, Kym R.
Moreau, Hélène D.
Garcia, Zacarias
Lemaître, Fabrice
Bouvier, Isabelle
Albert, Matthew L.
Bousso, Philippe
Source :
Cell Reports; November 2012, Vol. 2 Issue: 5 p1438-1447, 10p
Publication Year :
2012

Abstract

Contraction is a critical phase of immunity whereby the vast majority of effector T cells die by apoptosis, sparing a population of long-lived memory cells. Where, when, and why contraction occurs has been difficult to address directly due in large part to the rapid clearance of apoptotic T cells in vivo. To circumvent this issue, we introduced a genetically encoded reporter for caspase-3 activity into naive T cells to identify cells entering the contraction phase. Using two-photon imaging, we found that caspase-3 activity in T cells was maximal at the peak of the response and was associated with loss of motility followed minutes later by cell death. We demonstrated that contraction is a widespread process occurring uniformly in all organs tested and targeting phenotypically diverse T cells. Importantly, we identified a critical window of time during which antigen encounters act to antagonize T cell apoptosis, supporting a causal link between antigen clearance and T cell contraction. Our results offer insight into a poorly explored phase of immunity and provide a versatile methodology to study apoptosis during the development or function of a variety of immune cells in vivo.

Details

Language :
English
ISSN :
22111247
Volume :
2
Issue :
5
Database :
Supplemental Index
Journal :
Cell Reports
Publication Type :
Periodical
Accession number :
ejs29030192
Full Text :
https://doi.org/10.1016/j.celrep.2012.10.015