title: Dissecting T cell contraction in vivo using a genetically encoded reporter of apoptosis.
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.
authors.affiliation: Institut Pasteur, Dynamics of Immune Responses Unit, 75015 Paris, France; INSERM U668, 75015 Paris, France.
authors.forename: Kym R
authors.initials: KR
authors.lastname: Garrod
authors.forename: Hélène D
authors.initials: HD
authors.lastname: Moreau
authors.forename: Zacarias
authors.initials: Z
authors.lastname: Garcia
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lemaître
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bouvier
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert
authors.forename: Philippe
authors.initials: P
authors.lastname: Bousso
mesh_terms: D000818:Animals; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D053148:Caspase 3 / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D017930:Genes, Reporter; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D053148:Caspase 3